1c8p: Difference between revisions

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[[Image:1c8p.gif|left|200px]]<br />

[[Image:1c8p.gif|left|200px]]<br /><applet load="1c8p" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1c8p" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1c8p" />

'''NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS'''<br />

==Overview==

The haemopoietic cytokines, granulocyte-macrophage colony-stimulating, factor, interleukin-3 and interleukin-5 bind to cell-surface receptors, comprising ligand-specific alpha-chains and a shared beta-chain. The, beta-chain is the critical signalling subunit of the receptor and its, fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation, can lead to ligand-independent activation of the receptor. We have, determined the NMR solution structure of the isolated human fourth domain, of the beta-chain. The protein has a fibronectin type III fold with a, well-defined hydrophobic core and is stabilised by an extensive network of, pi-cation interactions involving Trp and Arg side-chains, including two, Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where, Xaa is any amino acid) that is found in many cytokine receptors. Most of, the residues implicated in factor-independent mutants localise to the, rigid core of the domain or the pi-cation stack. The loops between the B, and C, and the F and G strands, that contain residues important for, interactions with cytokines, lie adjacent at the membrane-distal end of, the domain, consistent with their being involved cooperatively in binding, cytokines. The elucidation of the structure of the cytokine-binding domain, of the beta-chain provides insight into the cytokine-dependent and, factor-independent activation of the receptor.

The haemopoietic cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 bind to cell-surface receptors comprising ligand-specific alpha-chains and a shared beta-chain. The beta-chain is the critical signalling subunit of the receptor and its fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation can lead to ligand-independent activation of the receptor. We have determined the NMR solution structure of the isolated human fourth domain of the beta-chain. The protein has a fibronectin type III fold with a well-defined hydrophobic core and is stabilised by an extensive network of pi-cation interactions involving Trp and Arg side-chains, including two Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where Xaa is any amino acid) that is found in many cytokine receptors. Most of the residues implicated in factor-independent mutants localise to the rigid core of the domain or the pi-cation stack. The loops between the B and C, and the F and G strands, that contain residues important for interactions with cytokines, lie adjacent at the membrane-distal end of the domain, consistent with their being involved cooperatively in binding cytokines. The elucidation of the structure of the cytokine-binding domain of the beta-chain provides insight into the cytokine-dependent and factor-independent activation of the receptor.

==About this Structure==

1C8P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure ~~superseeds~~ the now removed PDB entry 1D4Q. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1C8P OCA].

1C8P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1D4Q. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C8P OCA].

==Reference==

Line 14:

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Andrea, R.J.D.]]

[[Category: Andrea, R J.D.]]

[[Category: Bagley, C.J.]]

[[Category: Bagley, C J.]]

[[Category: Booker, G.W.]]

[[Category: Booker, G W.]]

[[Category: Gaunt, C.]]

[[Category: Lopez, A.F.]]

[[Category: Lopez, A F.]]

[[Category: Mulhern, T.D.]]

[[Category: Mulhern, T D.]]

[[Category: Vadas, M.A.]]

[[Category: Vadas, M A.]]

[[Category: Vandeleur, L.]]

[[Category: beta sandwich]]

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[[Category: fn3 domain]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 16:18:~~22 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:33 2008''

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-[[Image:1c8p.gif|left|200px]]<br />
+[[Image:1c8p.gif|left|200px]]<br /><applet load="1c8p" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1c8p" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1c8p" />
 '''NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS'''<br />
 ==Overview==
-The haemopoietic cytokines, granulocyte-macrophage colony-stimulating, factor, interleukin-3 and interleukin-5 bind to cell-surface receptors, comprising ligand-specific alpha-chains and a shared beta-chain. The, beta-chain is the critical signalling subunit of the receptor and its, fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation, can lead to ligand-independent activation of the receptor. We have, determined the NMR solution structure of the isolated human fourth domain, of the beta-chain. The protein has a fibronectin type III fold with a, well-defined hydrophobic core and is stabilised by an extensive network of, pi-cation interactions involving Trp and Arg side-chains, including two, Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where, Xaa is any amino acid) that is found in many cytokine receptors. Most of, the residues implicated in factor-independent mutants localise to the, rigid core of the domain or the pi-cation stack. The loops between the B, and C, and the F and G strands, that contain residues important for, interactions with cytokines, lie adjacent at the membrane-distal end of, the domain, consistent with their being involved cooperatively in binding, cytokines. The elucidation of the structure of the cytokine-binding domain, of the beta-chain provides insight into the cytokine-dependent and, factor-independent activation of the receptor.
+The haemopoietic cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 bind to cell-surface receptors comprising ligand-specific alpha-chains and a shared beta-chain. The beta-chain is the critical signalling subunit of the receptor and its fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation can lead to ligand-independent activation of the receptor. We have determined the NMR solution structure of the isolated human fourth domain of the beta-chain. The protein has a fibronectin type III fold with a well-defined hydrophobic core and is stabilised by an extensive network of pi-cation interactions involving Trp and Arg side-chains, including two Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where Xaa is any amino acid) that is found in many cytokine receptors. Most of the residues implicated in factor-independent mutants localise to the rigid core of the domain or the pi-cation stack. The loops between the B and C, and the F and G strands, that contain residues important for interactions with cytokines, lie adjacent at the membrane-distal end of the domain, consistent with their being involved cooperatively in binding cytokines. The elucidation of the structure of the cytokine-binding domain of the beta-chain provides insight into the cytokine-dependent and factor-independent activation of the receptor.
 ==About this Structure==
-C8P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1D4Q. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C8P OCA].
+C8P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1D4Q. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C8P OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Andrea, R.J.D.]]
+[[Category: Andrea, R J.D.]]
-[[Category: Bagley, C.J.]]
+[[Category: Bagley, C J.]]
-[[Category: Booker, G.W.]]
+[[Category: Booker, G W.]]
 [[Category: Gaunt, C.]]
-[[Category: Lopez, A.F.]]
+[[Category: Lopez, A F.]]
-[[Category: Mulhern, T.D.]]
+[[Category: Mulhern, T D.]]
-[[Category: Vadas, M.A.]]
+[[Category: Vadas, M A.]]
 [[Category: Vandeleur, L.]]
 [[Category: beta sandwich]]
@@ Line 26: / Line 25: @@
 [[Category: fn3 domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:18:22 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:33 2008''