2pf5
From Proteopedia
(New page: 200px<br /> <applet load="2pf5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pf5, resolution 1.90Å" /> '''Crystal Structure o...) |
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| - | [[Image:2pf5.gif|left|200px]]<br /> | + | [[Image:2pf5.gif|left|200px]]<br /><applet load="2pf5" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2pf5, resolution 1.90Å" /> | caption="2pf5, resolution 1.90Å" /> | ||
'''Crystal Structure of the Human TSG-6 Link Module'''<br /> | '''Crystal Structure of the Human TSG-6 Link Module'''<br /> | ||
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| + | ==Overview== | ||
| + | Tumour necrosis factor-stimulated gene-6 (TSG-6) is a, glycosaminoglycan-binding protein expressed during inflammatory and, inflammation-like processes. Previously NMR structures were calculated for, the Link module of TSG-6 (Link_TSG6) in its free state and when bound to, an octasaccharide of hyaluronan (HA(8)). Heparin was found to compete for, HA binding even though it interacts at a site that is distinct from the, HA-binding surface. Here we present crystallography data on the free, protein, and (15)N NMR relaxation data for the uncomplexed and HA(8)-bound, forms of Link_TSG6. Although the Link module is comparatively rigid, overall, the free protein shows a high degree of mobility in the, beta4/beta5 loop and at the Cys47-Cys68 disulfide bond, both of which are, regions involved in HA binding. When bound to HA(8), this dynamic, behaviour is dampened, but not eliminated, suggesting a degree of dynamic, matching between the protein and sugar that may decrease the entropic, penalty of complex formation. A further highly dynamic residue is Lys54, which is distant from the HA-binding site, but was previously shown to be, involved in heparin binding. When HA is bound, Lys54 becomes less mobile, providing evidence for an allosteric effect linking the HA and, heparin-binding sites. A mechanism is suggested involving the beta2-strand, and alpha2-helix. The crystal structure of free Link_TSG6 contains five, molecules in the asymmetric unit that are highly similar to the NMR, structure and support the dynamic behaviour seen near the HA-binding site:, they show little or no electron density for the beta4/beta5 loop and, display multiple conformations for the Cys47-Cys68 disulfide bond. The, crystal structures were used in docking calculations with heparin. An, extended interface between a Link_TSG6 dimer and heparin 11-mer was, identified that is in excellent agreement with previous mutagenesis and, calorimetric data, providing the basis for further investigation of this, interaction. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2PF5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and 2PE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2PF5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=2PE:'>2PE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PF5 OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Plasticity of the TSG-6 HA-binding loop and mobility in the TSG-6-HA complex revealed by NMR and X-ray crystallography., Higman VA, Blundell CD, Mahoney DJ, Redfield C, Noble ME, Day AJ, J Mol Biol. 2007 Aug 17;371(3):669-84. Epub 2007 Jun 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17585936 17585936] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: 2PE]] | [[Category: 2PE]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| + | [[Category: cell adhesion]] | ||
[[Category: link module; hyaluronan-binding domain; alpha/beta domain]] | [[Category: link module; hyaluronan-binding domain; alpha/beta domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:56:58 2008'' |
Revision as of 09:56, 23 January 2008
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Crystal Structure of the Human TSG-6 Link Module
Overview
Tumour necrosis factor-stimulated gene-6 (TSG-6) is a, glycosaminoglycan-binding protein expressed during inflammatory and, inflammation-like processes. Previously NMR structures were calculated for, the Link module of TSG-6 (Link_TSG6) in its free state and when bound to, an octasaccharide of hyaluronan (HA(8)). Heparin was found to compete for, HA binding even though it interacts at a site that is distinct from the, HA-binding surface. Here we present crystallography data on the free, protein, and (15)N NMR relaxation data for the uncomplexed and HA(8)-bound, forms of Link_TSG6. Although the Link module is comparatively rigid, overall, the free protein shows a high degree of mobility in the, beta4/beta5 loop and at the Cys47-Cys68 disulfide bond, both of which are, regions involved in HA binding. When bound to HA(8), this dynamic, behaviour is dampened, but not eliminated, suggesting a degree of dynamic, matching between the protein and sugar that may decrease the entropic, penalty of complex formation. A further highly dynamic residue is Lys54, which is distant from the HA-binding site, but was previously shown to be, involved in heparin binding. When HA is bound, Lys54 becomes less mobile, providing evidence for an allosteric effect linking the HA and, heparin-binding sites. A mechanism is suggested involving the beta2-strand, and alpha2-helix. The crystal structure of free Link_TSG6 contains five, molecules in the asymmetric unit that are highly similar to the NMR, structure and support the dynamic behaviour seen near the HA-binding site:, they show little or no electron density for the beta4/beta5 loop and, display multiple conformations for the Cys47-Cys68 disulfide bond. The, crystal structures were used in docking calculations with heparin. An, extended interface between a Link_TSG6 dimer and heparin 11-mer was, identified that is in excellent agreement with previous mutagenesis and, calorimetric data, providing the basis for further investigation of this, interaction.
About this Structure
2PF5 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Plasticity of the TSG-6 HA-binding loop and mobility in the TSG-6-HA complex revealed by NMR and X-ray crystallography., Higman VA, Blundell CD, Mahoney DJ, Redfield C, Noble ME, Day AJ, J Mol Biol. 2007 Aug 17;371(3):669-84. Epub 2007 Jun 2. PMID:17585936
Page seeded by OCA on Wed Jan 23 11:56:58 2008
