4wjk: Difference between revisions
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<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=4wjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wjk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wjk RCSB], [http://www.ebi.ac.uk/pdbsum/4wjk PDBsum]</span></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=4wjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wjk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wjk RCSB], [http://www.ebi.ac.uk/pdbsum/4wjk PDBsum]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Integrin alpha5beta1 binds to an Arg-Gly-Asp (RGD) motif in its ligand fibronectin. We report high-resolution crystal structures of a four-domain alpha5beta1 headpiece fragment, alone or with RGD peptides soaked into crystals, and RGD peptide affinity measurements. The headpiece crystallizes in a closed conformation essentially identical to that seen previously for alpha5beta1 complexed with a Fab that allosterically inhibits ligand binding by stabilizing the closed conformation. Soaking experiments show that binding of cyclic RGD peptide with 20-fold higher affinity than a linear RGD peptide induces conformational change in the beta1-subunit betaI domain to a state that is intermediate between closed (low affinity) and open (high affinity). In contrast, binding of a linear RGD peptide induces no shape shifting. However, linear peptide binding induces shape shifting when Ca2+ is depleted during soaking. Ca2+ bound to the adjacent to metal ion-dependent adhesion site (ADMIDAS), at the locus of shape shifting, moves and decreases in occupancy, correlating with an increase in affinity for RGD measured when Ca2+ is depleted. The results directly demonstrate that Ca2+ binding to the ADMIDAS stabilizes integrins in the low-affinity, closed conformation. Comparisons in affinity between four-domain and six-domain headpiece constructs suggest that flexible integrin leg domains contribute to conformational equilibria. High-resolution views of the hybrid domain interface with the plexin-semaphorin-integrin (PSI) domain in different orientations show a ball-and-socket joint with a hybrid domain Arg side chain that rocks in a PSI domain socket lined with carbonyl oxygens. | |||
Metal ion and ligand binding of integrin alpha5beta1.,Xia W, Springer TA Proc Natl Acad Sci U S A. 2014 Dec 4. pii: 201420645. PMID:25475857<ref>PMID:25475857</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
<references/> | |||
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</StructureSection> | </StructureSection> | ||