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| | ==Crystal Structure of the Human TSG-6 Link Module== | | ==Crystal Structure of the Human TSG-6 Link Module== |
| - | <StructureSection load='2pf5' size='340' side='right' caption='[[2pf5]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2pf5' size='340' side='right'caption='[[2pf5]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pf5]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PF5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PF5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pf5]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PF5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFAIP6, TSG6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFAIP6, TSG6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pf5 OCA], [http://pdbe.org/2pf5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pf5 RCSB], [http://www.ebi.ac.uk/pdbsum/2pf5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pf5 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pf5 OCA], [https://pdbe.org/2pf5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pf5 RCSB], [https://www.ebi.ac.uk/pdbsum/2pf5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pf5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TSG6_HUMAN TSG6_HUMAN]] Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis. | + | [[https://www.uniprot.org/uniprot/TSG6_HUMAN TSG6_HUMAN]] Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Day, A J]] | | [[Category: Day, A J]] |
| | [[Category: Higman, V A]] | | [[Category: Higman, V A]] |
| Structural highlights
Function
[TSG6_HUMAN] Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Higman VA, Blundell CD, Mahoney DJ, Redfield C, Noble ME, Day AJ. Plasticity of the TSG-6 HA-binding loop and mobility in the TSG-6-HA complex revealed by NMR and X-ray crystallography. J Mol Biol. 2007 Aug 17;371(3):669-84. Epub 2007 Jun 2. PMID:17585936 doi:10.1016/j.jmb.2007.05.073
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