View source for 4wk0


==Metal Ion and Ligand Binding of Integrin==
<StructureSection load='4wk0' size='340' side='right'caption='[[4wk0]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wk0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WK0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4wk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wk0 OCA], [https://pdbe.org/4wk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wk0 RCSB], [https://www.ebi.ac.uk/pdbsum/4wk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wk0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ITA5_HUMAN ITA5_HUMAN] Integrin alpha-5/beta-1 is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wk0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Springer TA]]
[[Category: Xia W]]