1c8p
From Proteopedia
(New page: 200px<br /> <applet load="1c8p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c8p" /> '''NMR STRUCTURE OF THE LIGAND BINDING DOMAIN ...) |
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'''NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS'''<br /> | '''NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The haemopoietic cytokines, granulocyte-macrophage colony-stimulating | + | 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== | ==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 | + | 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== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Andrea, R | + | [[Category: Andrea, R J.D.]] |
| - | [[Category: Bagley, C | + | [[Category: Bagley, C J.]] |
| - | [[Category: Booker, G | + | [[Category: Booker, G W.]] |
[[Category: Gaunt, C.]] | [[Category: Gaunt, C.]] | ||
| - | [[Category: Lopez, A | + | [[Category: Lopez, A F.]] |
| - | [[Category: Mulhern, T | + | [[Category: Mulhern, T D.]] |
| - | [[Category: Vadas, M | + | [[Category: Vadas, M A.]] |
[[Category: Vandeleur, L.]] | [[Category: Vandeleur, L.]] | ||
[[Category: beta sandwich]] | [[Category: beta sandwich]] | ||
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[[Category: fn3 domain]] | [[Category: fn3 domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:33 2008'' |
Revision as of 10:03, 21 February 2008
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NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS
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.
About this Structure
1C8P is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1D4Q. Full crystallographic information is available from OCA.
Reference
The solution structure of the cytokine-binding domain of the common beta-chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5., Mulhern TD, Lopez AF, D'Andrea RJ, Gaunt C, Vandeleur L, Vadas MA, Booker GW, Bagley CJ, J Mol Biol. 2000 Apr 7;297(4):989-1001. PMID:10736232
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