Sandbox207: Difference between revisions

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==CRP, C-reactive Protein==

::The C Reactive Protein is a protein of the '''acute phase''', the first described, exclusively synthetized by the liver.

:The C Reactive Protein is a protein of the '''acute phase''', the first described, exclusively synthetized by the liver.

:The CRP was first isolated by '''Tillett and France in 1930''', in patients' serum presenting an acute inflammation. This protein reacted to the '''polysaccharide C''' of the pneumocoque, that is where its name comes from. [http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <1>]

::The CRP contributes to innate host defense, and plays an important role in inflammatory reactions. It can bind to specific molecular configurations typically exposed during cell death or found on the surfaces of pathogens. It is used as '''biological marker''' to reveal an inflammatory reaction and tissue damage. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]

:The CRP contributes to innate host defense, and plays an important role in inflammatory reactions. It can bind to specific molecular configurations typically exposed during cell death or found on the surfaces of pathogens. It is used as '''biological marker''' to reveal an inflammatory reaction and tissue damage. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]

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===Detailed strucutre===

:Each protomer consists of two '''anti-parallel β sheets''' (the lectin fold) with an '''α helix''' on the effector face of the protein. The ligand biding site is located on the concave face of the protein, and is composed of loops with 2 calcium ions bound 4 Å apart by protein side-chains.

:Each protomer consists of two '''anti-parallel β sheets''' (the lectin fold) with an '''α helix''' on the effector face of the protein. The ligand biding site is located on the concave face of the protein, and is composed of loops with '''2 calcium ions''' bound 4 Å apart by protein side-chains.

:The recognition face contains the which consists of two coordinated calcium ions next to a hydrophobic pocket in which the phosphocholine stays.

:The recognition face contains the _________ which consists of two coordinated calcium ions next to a '''hydrophobic pocket''' in which the phosphocholine stays.

:There are ~~interpromoter~~ interactions between the subunits: three salt bridges are included and the 115-123 loop of one protomer and the 40-42 and 197-202 regions of adjacent protomers are involved. Moreover, the subunits ~~are capable to~~ rotate by 15-20° around an axis parallel to the central alpha-helix.

:There are interprotomer interactions between the subunits: '''three salt bridges''' are included and the 115-123 loop of one protomer and the 40-42 and 197-202 regions of adjacent protomers are involved. Moreover, the subunits can rotate by 15-20° around an axis parallel to the central alpha-helix.

[[Image:Image1.jpg|500px|right|thumb| '''Molecular structure and morphology of human CRP.'''

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(a) Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows). (b) Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer. (c) Space-filling model of the CRP molecule, showing a single phosphocholine molecule located in the ligand-binding site of each protomer.[http://www.jci.org/articles/view/18921 <3>]]]

: Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore ~~bringin~~ the bound Ca2+ further away from it. On each subunit, we can find phosphocholine bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety, the phosphocholine can interact with the two protein-bound ions.

: Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore bringing the bound Ca2+ further away from it. On each subunit, we can find phosphocholine bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety, the phosphocholine can interact with the two protein-bound ions.

:Moreover, the structure of CRP is different in diseased patients. Indeed, in some pathological conditions, the Human CRP is glycosylated. Analysis of the structure showed the systematic absence of two peptide fragments, one at the N-terminus (loop 1-6) in all patients, the other near the C-terminus (loop 189-191) in patients with osteogenic sarcoma and Cushing's syndrome. In an undiseased individual, glycosylation sites are inacessible due to the presence of the N-terminal. The loss of these two fragments exposed two potential glycosylation sites on a cleft door. The functional areas of the pentraxin structure remains the same since the Ca2+ and phosphocholine sites are on the opposite site of the pentraxin molecule. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]

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@@ Line 10: / Line 10: @@
 ==CRP, C-reactive Protein==
-::The C Reactive Protein is a protein of the '''acute phase''', the first described, exclusively synthetized by the liver.
+:The C Reactive Protein is a protein of the '''acute phase''', the first described, exclusively synthetized by the liver.
 :The CRP was first isolated by '''Tillett and France in 1930''', in patients' serum presenting an acute inflammation. This protein reacted to the '''polysaccharide C''' of the pneumocoque, that is where its name comes from. [http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <1>]
-::The CRP contributes to innate host defense, and plays an important role in inflammatory reactions. It can bind to specific molecular configurations typically exposed during cell death or found on the surfaces of pathogens. It is used as '''biological marker''' to reveal an inflammatory reaction and tissue damage. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]
+:The CRP contributes to innate host defense, and plays an important role in inflammatory reactions. It can bind to specific molecular configurations typically exposed during cell death or found on the surfaces of pathogens. It is used as '''biological marker''' to reveal an inflammatory reaction and tissue damage. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]
@@ Line 31: / Line 31: @@
 ===Detailed strucutre===
-:Each protomer consists of two '''anti-parallel β sheets''' (the lectin fold) with an '''α helix''' on the effector face of the protein. The ligand biding site is located on the concave face of the protein, and is composed of loops with 2 calcium ions bound 4 Å apart by protein side-chains.
+:Each protomer consists of two '''anti-parallel β sheets''' (the lectin fold) with an '''α helix''' on the effector face of the protein. The ligand biding site is located on the concave face of the protein, and is composed of loops with '''2 calcium ions''' bound 4 Å apart by protein side-chains.
-:The recognition face contains the which consists of two coordinated calcium ions next to a hydrophobic pocket in which the phosphocholine stays.
+:The recognition face contains the _________ which consists of two coordinated calcium ions next to a '''hydrophobic pocket''' in which the phosphocholine stays.
-:There are interpromoter interactions between the subunits: three salt bridges are included and the 115-123 loop of one protomer and the 40-42 and 197-202 regions of adjacent protomers are involved. Moreover, the subunits are capable to rotate by 15-20° around an axis parallel to the central alpha-helix.
+:There are interprotomer interactions between the subunits: '''three salt bridges''' are included and the 115-123 loop of one protomer and the 40-42 and 197-202 regions of adjacent protomers are involved. Moreover, the subunits can rotate by 15-20° around an axis parallel to the central alpha-helix.
 [[Image:Image1.jpg|500px|right|thumb| '''Molecular structure and morphology of human CRP.'''
@@ Line 39: / Line 39: @@
 (a) Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows). (b) Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer. (c) Space-filling model of the CRP molecule, showing a single phosphocholine molecule located in the ligand-binding site of each protomer.[http://www.jci.org/articles/view/18921 <3>]]]
-: Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore bringin the bound Ca2+ further away from it. On each subunit, we can find phosphocholine bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety, the phosphocholine can interact with the two protein-bound ions.
+: Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore bringing the bound Ca2+ further away from it. On each subunit, we can find phosphocholine bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety, the phosphocholine can interact with the two protein-bound ions.
 :Moreover, the structure of CRP is different in diseased patients. Indeed, in some pathological conditions, the Human CRP is glycosylated. Analysis of the structure showed the systematic absence of two peptide fragments, one at the N-terminus (loop 1-6) in all patients, the other near the C-terminus (loop 189-191) in patients with osteogenic sarcoma and Cushing's syndrome. In an undiseased individual, glycosylation sites are inacessible due to the presence of the N-terminal. The loss of these two fragments exposed two potential glycosylation sites on a cleft door. The functional areas of the pentraxin structure remains the same since the Ca2+ and phosphocholine sites are on the opposite site of the pentraxin molecule. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]