Proteopedia - User contributions [en]

Interleukin-1 beta

2013-12-18T16:45:59Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

The molecule contains 12 antiparallel β-strands. The molecule has internal pseudo threefold symmetry with the molecule representing a conical barrel with a shallow open face on one end and a closed face on the other. The amino and carboxy termini are located at the "open end" of the barrel and they are close to each other. 24 hydrophobic side chains are present in the inner surface of the barrel and polar residues are found to be exposed on both the ends of the barrel. More detail structure information could be found in reference[4].

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The complex has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. In the <scene name='57/571319/Scene_2/3'>complex</scene>, domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel[5]. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6].

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-18T16:40:04Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

The molecule contains 12 antiparallel β-strands. The molecule has internal pseudo threefold symmetry with the molecule representing a conical barrel with a shallow open face on one end and a closed face on the other. The amino and carboxy termini are close to each other at the "open end" of the barrel. Two of the five 1-hairpins in this molecule are located in the "open end" and three at the "closed end". 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues. More detail structure information could be found in reference[4].

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The complex has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. In the <scene name='57/571319/Scene_2/3'>complex</scene>, domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel[5]. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6].

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-18T16:37:06Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

The molecule contains 12 antiparallel β-strands. The molecule has internal pseudo threefold symmetry with the molecule represents a conical barrel with a shallow open face on one end and a closed face on the other. The amino and carboxy termini are close to each other at the "open end" of the barrel. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues. More detail structure information could be found in reference[4].

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The complex has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. In the <scene name='57/571319/Scene_2/3'>complex</scene>, domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel[5]. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6].

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-18T16:29:17Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

"The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues."[4]

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The complex has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. In the <scene name='57/571319/Scene_2/3'>complex</scene>, domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel[5]. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6].

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-18T16:15:57Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]"The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues."

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The complex has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. In the <scene name='57/571319/Scene_2/3'>complex</scene>, domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel[5]. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-18T16:03:30Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]"The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues."

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T23:30:25Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.
The <scene name='57/571319/Scene_3/3'>Interleukin-1 beta receptor accessory protein</scene> also could be seen.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Interleukin-1 beta

2013-12-06T23:22:16Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T23:20:54Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>click here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T23:20:01Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you <scene name='57/571319/Scene_3/2'>'''click here'''</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and blue, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T23:18:25Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors('''IL-1R''') first bind their corresponding cytokine ligands('''IL-1β''') and then engage the accessory receptor('''IL-1RAcP''') (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved area was showed when you click <scene name='57/571319/Scene_3/2'>here</scene>. The insert are ligands(IL-1β), which are present as conserved structure as well as green ribbon. The two IL-1Rs and two IL-1RAcPs are colored as purple and green, respectively.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T23:11:31Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

The dimer complex with conserved areawas showed when you click <scene name='57/571319/Scene_3/2'>here</scene>.

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

CBI Molecules

2013-12-06T20:19:07Z

Huan He:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2013: CBI Molecules are due 12/4/13 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2013" or "Revised 2013". For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: New Fall 2012!! '''[[Molecular Playground/OmpG]]''', Christina Chisholm
: New Fall 2013!! '''[[Molecular Playground/ClyA]]''', Bib Yang

[http://openwetware.org/wiki/Chien Chien Lab]

New Fall 2013! : **'''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: New Fall 2013!! '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill

: '''[[Molecular Playground/[[Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: New Fall 2013!! '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham
: New Fall 2012!! '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: Updated Fall 2012!! '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez

[http://people.chem.umass.edu/mholden/ Holden Lab]

: New Fall 2012!! '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

New 2013! '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]''', Chengfeng Ren

: Updated Fall 2012!! ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

: Updated Fall 2013!! '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky

: Updated Fall 2012!! '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas
:: Best CBI Molecule Proteopedia Page 2010

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: Updated Fall 2013!! '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr
: '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

[http://www.peytonlab.org/ Peyton Lab]
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman
: New Fall 2013! '''[[Molecular Playground/MMP14]]''', Lauren Jansen

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[http://http://www.umass.edu/schiffman/ Schiffman Lab]
:New Fall 2013! '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger

[https://elements.chem.umass.edu/schnarrlab/ Schnarr Lab]

: New Fall 2012!! '''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: New Fall 2012!! '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab
: New Fall 2013!! '''[[Interleukin-1 beta]]''', Huan He

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: New Fall 2012!! '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

: New Fall 2012!! '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2013: Complete steps 1-2 by 10/18, and bring your computer to the CBI Molecule Workshop on Wed 10/23 in ISB 321.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

1. If you don't already have one, request a Proteopedia account and log in.

2. Read through the rest of the instructions and look at any existing CBI Molecules from your research group. Talk with other Chalk Talk students in your research group and think about how you can make a new or improved CBI Molecule related to your group's research. Develop ideas for the scenes you wish to show. You will work learn how to make scenes during the workshop.

3. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

4. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2013" or "revised 2013".

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

Interleukin-1 beta

2013-12-06T20:17:22Z

Huan He: New page: == Interleukin-1 beta(IL-1β) == <Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' /> IL-1β along with IL-1α cyt...

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

CBI Molecules

2013-12-06T20:14:18Z

Huan He:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2013: CBI Molecules are due 12/4/13 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2013" or "Revised 2013". For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: New Fall 2012!! '''[[Molecular Playground/OmpG]]''', Christina Chisholm
: New Fall 2013!! '''[[Molecular Playground/ClyA]]''', Bib Yang

[http://openwetware.org/wiki/Chien Chien Lab]

New Fall 2013! : **'''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: New Fall 2013!! '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill

: '''[[Molecular Playground/[[Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: New Fall 2013!! '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham
: New Fall 2012!! '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: Updated Fall 2012!! '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez

[http://people.chem.umass.edu/mholden/ Holden Lab]

: New Fall 2012!! '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

New 2013! '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]''', Chengfeng Ren

: Updated Fall 2012!! ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

: Updated Fall 2013!! '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky

: Updated Fall 2012!! '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas
:: Best CBI Molecule Proteopedia Page 2010

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: Updated Fall 2013!! '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr
: '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

[http://www.peytonlab.org/ Peyton Lab]
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman
: New Fall 2013! '''[[Molecular Playground/MMP14]]''', Lauren Jansen

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[http://http://www.umass.edu/schiffman/ Schiffman Lab]
:New Fall 2013! '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger

[https://elements.chem.umass.edu/schnarrlab/ Schnarr Lab]

: New Fall 2012!! '''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: New Fall 2012!! '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab
: New Fall 2013!! '''[[Huan He/Sandbox1]]''', Huan He

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: New Fall 2012!! '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

: New Fall 2012!! '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2013: Complete steps 1-2 by 10/18, and bring your computer to the CBI Molecule Workshop on Wed 10/23 in ISB 321.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

1. If you don't already have one, request a Proteopedia account and log in.

2. Read through the rest of the instructions and look at any existing CBI Molecules from your research group. Talk with other Chalk Talk students in your research group and think about how you can make a new or improved CBI Molecule related to your group's research. Develop ideas for the scenes you wish to show. You will work learn how to make scenes during the workshop.

3. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

4. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2013" or "revised 2013".

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

Huan He/Sandbox1

2013-12-06T20:06:40Z

Huan He: /* Clinical significance */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Also, since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs[5].
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T20:04:31Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here[5]： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T20:02:11Z

Huan He: /* Reference */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1] Carl J. March, '''Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs''',[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2] Cerretti DP,'''Molecular cloning of the interleukin-1 beta converting enzyme''',[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3] Mizutani H, '''Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase'''.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4] B Veerapandian, '''Structure and function of interleukin-1, based on crystallographic and modeling studies''',[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5] Guy P. A. Vigers, '''Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β''',
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6] Christoph Thomas, '''Structure of the activating IL-1 receptor signaling complex''',[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

[7] Hou J, '''Design of a superior cytokine antagonist for topical ophthalmic use''',[http://www.pnas.org/content/110/10/3913.full.pdf Proc Natl Acad Sci USA,2013,110,3913-3918.]

Huan He/Sandbox1

2013-12-06T19:58:33Z

Huan He: /* Clinical significance */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]
For example, in this paper[7], the author therapeutically designed a superior cytokine antagonist(EBI-005, optimized receptor antagonist chimerized with IL-1β and IL-1Ra) for topical ophthalmic use.

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Cerretti DP,Molecular cloning of the interleukin-1 beta converting enzyme,[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:42:01Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> 3D structure was showed here, and the cartoon (right) showed the formation of the ternary complex paradigm,the primary receptors first bind their corresponding cytokine ligands and then engage the accessory receptor (which is incapable of binding cytokines by itself). The overall ternary architecture of the IL-1β–IL-1RI–IL-1RAcP signaling complex has the cytoplasmic TIR domain necessary for signal transduction. The IL-1RI-IL-1RAcP interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[6]

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Cerretti DP,Molecular cloning of the interleukin-1 beta converting enzyme,[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:14:01Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[4]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Cerretti DP,Molecular cloning of the interleukin-1 beta converting enzyme,[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:13:16Z

Huan He: /* Reference */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Cerretti DP,Molecular cloning of the interleukin-1 beta converting enzyme,[http://www.sciencemag.org/content/256/5053/97.full.pdf?sid=7e984f96-269f-4713-a25e-5f5f5d8188f8 Science,1992,256,97-100.]

[3]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[4]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[5]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[6]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:08:29Z

Huan He: /* Interleukin-1 beta(IL-1β) */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme[2]) to form IL-1 active species(17KDa)[3]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[3]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[4]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[5]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:05:59Z

Huan He: /* Interleukin-1 beta(IL-1β) */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species(17KDa)[2]. The active mature IL-1 cytokines could mediate a large range of biological activities such as innate and adaptive immunity as well as bio-components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[3]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[4]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[5]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:01:34Z

Huan He: /* Clinical significance */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species(17KDa)[2]. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[3].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[5]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[3]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[4]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[5]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T19:00:57Z

Huan He: /* Reference */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species(17KDa)[2]. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[3].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]Carl J. March,Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs,[http://www.nature.com/nature/journal/v315/n6021/abs/315641a0.html Nature,1985,315,641-647.]

[2]Mizutani H, Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.[http://jem.rupress.org/content/174/4/821.long J Exp Med.,1991,174,821-825.]

[3]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[4]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[5]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T18:52:01Z

Huan He: /* Interleukin-1 beta(IL-1β) */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α cytokines secreted from local inflammatory cells, are belong to IL-1 family.[1] The former is dominate (90% of Interleukin-1) and the two cytokines could be distinguished by the cells with which they interact. IL-1β precursor(31KDa) need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species(17KDa)[2]. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[3].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T17:08:52Z

Huan He: /* Clinical significance */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
Why are people interested in IL-1? Because IL-1 cytokines family are usually over-expressed at tumor sites or inflammatory, these cytokines could be used as bio-markers to help diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T17:06:31Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T17:04:47Z

Huan He: /* Human Interleukin-1 Beta */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2][[http://www.proteopedia.org/wiki/index.php?title=Huan_He/Sandbox1&action=edit&section=4]]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T17:00:10Z

Huan He: /* Reference */

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J.1992,62,112–115.]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β,
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology,2012,19,455–457.]

Huan He/Sandbox1

2013-12-06T16:58:22Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β[4] . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J. 1992 April; 62(1): 112–115. ]

[3]Guy P. A. Vigers,Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β
[http://www.nature.com/nature/journal/v386/n6621/abs/386190a0.html Nature 1997,386,190-194.]

[4]Christoph Thomas, Structure of the activating IL-1 receptor signaling complex,[http://www.nature.com.silk.library.umass.edu/nsmb/journal/v19/n4/full/nsmb.2260.html Nature Structural& Molecular Biology 19,455–457(2012)]

Huan He/Sandbox1

2013-12-06T16:50:07Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.
<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]

[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J. 1992 April; 62(1): 112–115. ]

[3]

[4]

Huan He/Sandbox1

2013-12-06T16:48:40Z

Huan He:

== Interleukin-1 beta(IL-1β) ==

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== Human Interleukin-1 Beta ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''

Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<scene name='57/571319/Scene1/1'>Human Interleukin-1 beta</scene> are present in the 3D structure. In the picture we could see <scene name='57/571319/Scene1/2'>helix</scene> was colored as purple and <scene name='57/571319/Scene1/2'>sheet</scene> was colored as blue, respectively. Most <scene name='57/571319/Scene1/3'>conserved area</scene> ,which is dark red color, was buried inside of the protein.

{{Template:ColorKey_ConSurf}}

'''TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA'''

[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane.

<scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]

Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.

'''STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX'''

[[Image:Ternary complex paradigm.png||250px|right|]]

<scene name='57/571319/Scene_3/1'> Interleukin-1 beta signal complex</scene> showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β . From the scenario, we

==Clinical significance==
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]

==Reference==
[1]
[2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J. 1992 April; 62(1): 112–115. ]
[3]
[4]

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== Interleukin-1 beta(IL-1β) ==

IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of [http://en.wikipedia.org/wiki/Acute-phase_protein acute phase proteins].
interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].

== HUMAN INTERLEUKIN-1 BETA ==

'''THREE-DIMENSIONAL STRUCTURE OF IL-1β'''
The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. Themolecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. The polypeptide a-carbon backbone of IL13, viewed perpendicular to the barrel axis, is shown in Fig. 1. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.

<Structure load='9ilb' size='400' frame='true' align='right' caption='HUMAN INTERLEUKIN-1 BETA' scene='57/571319/Scene1/1' />

<scene name='57/571319/Scene1/1'>HUMAN INTERLEUKIN-1 BETA</scene>

== TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA ==

<scene name='57/571319/Scene_2/2'>TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA</scene>

== STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX ==

<scene name='57/571319/Scene_3/1'>INTERLEUKIN-1BETA SIGNALING COMPLEX</scene>

[[Image:Ternary complex paradigm.png||250px|right|]]

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