View source for 5xpy


==Structural basis of kindlin-mediated integrin recognition and activation==
<StructureSection load='5xpy' size='340' side='right'caption='[[5xpy]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xpy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XPY 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]] 2.099&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5xpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpy OCA], [https://pdbe.org/5xpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xpy RCSB], [https://www.ebi.ac.uk/pdbsum/5xpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FERM2_MOUSE FERM2_MOUSE] Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.<ref>PMID:18174465</ref> <ref>PMID:18483218</ref> <ref>PMID:21378273</ref> 
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== Publication Abstract from PubMed ==
Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain-containing proteins, talins and kindlins, respectively, bind different regions of beta-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the beta1- and beta3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.

Structural basis of kindlin-mediated integrin recognition and activation.,Li H, Deng Y, Sun K, Yang H, Liu J, Wang M, Zhang Z, Lin J, Wu C, Wei Z, Yu C Proc Natl Acad Sci U S A. 2017 Jul 24. pii: 201703064. doi:, 10.1073/pnas.1703064114. PMID:28739949<ref>PMID:28739949</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5xpy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Li H]]
[[Category: Sun K]]
[[Category: Wei Z]]
[[Category: Yang H]]
[[Category: Yu C]]
[[Category: Zhang Z]]