View source for 2msu


==NMR structure of Kindlin-2 F2 339-358==
<StructureSection load='2msu' size='340' side='right'caption='[[2msu]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2msu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MSU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MSU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2msu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2msu OCA], [https://pdbe.org/2msu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2msu RCSB], [https://www.ebi.ac.uk/pdbsum/2msu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2msu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FERM2_HUMAN FERM2_HUMAN] 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:12679033</ref> <ref>PMID:18458155</ref> <ref>PMID:21325030</ref> <ref>PMID:22699938</ref> <ref>PMID:22030399</ref> <ref>PMID:22078565</ref> 
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== Publication Abstract from PubMed ==
ILK (integrin-linked kinase) is a distinct intracellular adaptor essential for integrin-mediated cell-extracellular matrix (ECM) adhesion, cell spreading, and migration. Acting as a major docking platform in focal adhesions (FAs), ILK engages many proteins to dynamically link integrins with cytoskeleton, but the underlying mechanism remains elusive. Here we have characterized the interaction of ILK with kindlin-2, a key regulator for integrin bi-directional signaling. We show that human kindlin-2 binds to human ILK with high affinity. Using systematic mapping approaches, we have identified a major ILK binding site involving a 20-residue (339-358) fragment in kindlin-2. NMR-based analysis reveals a helical conformation of this fragment which utilizes its leucine-rich surface to recognize the ILK pseudokinase domain in a mode that is distinct from another ILK pseudokinase domain binding protein, alpha-parvin. Structure-based mutational experiments further demonstrate that the kindlin-2 binding to ILK is crucial for the kindlin-2 localization to FAs and cell spreading (integrin outside-in signaling) but dispensable for the kindlin-2-mediated integrin activation (integrin inside-out signaling). These data define a specific mode of the kindlin-2/ILK interaction with mechanistic implications as to how it spatiotemporally mediates integrin signaling and cell adhesion.

Molecular basis of kindlin-2 binding to integrin-linked kinase (ILK) pseudokinase for regulating cell adhesion.,Fukuda K, Bledzka K, Yang J, Perera HD, Plow EF, Qin J J Biol Chem. 2014 Aug 25. pii: jbc.M114.596692. PMID:25160619<ref>PMID:25160619</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bledzka K]]
[[Category: Fukuda K]]
[[Category: Perera HD]]
[[Category: Yang J]]