6u4n

<StructureSection load='6u4n' size='340' side='right'caption='[[6u4n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[6u4n]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U4N FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6u4m|6u4m]]</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=6u4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u4n OCA], [http://pdbe.org/6u4n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u4n RCSB], [http://www.ebi.ac.uk/pdbsum/6u4n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u4n ProSAT]</span></td></tr>

[[http://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> [[http://www.uniprot.org/uniprot/PAXI_HUMAN PAXI_HUMAN]] Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion).

Activation of cell surface receptor integrin has been extensively studied as the first key step to trigger cell adhesion, but the subsequent events, widely regarded as integrin "outside-in" signaling to form supramolecular complexes (focal adhesions [FAs]) to promote dynamic cell adhesion, remain poorly elucidated. Integrin activator kindlin-2 was recently found to associate with paxillin in nascent FAs, implicating an early yet undefined integrin outside-in signaling event. Here we show structurally that kindlin-2 recognizes paxillin via a distinct interface involving the ubiquitin-like kindlin-2 F0 domain and the paxillin LIM4 domain. The interface is adjacent to the membrane binding site of kindlin-2 F0, suggesting a mechanism for kindlin-2 to recruit paxillin to the membrane-proximal site where FA assembly is initiated. Disruption of the interface impaired the localization of paxillin, causing strong defects in FA assembly and cell migration. These data unveil a structural basis of the kindlin-2/paxillin interaction in controlling dynamic cell adhesion.

 

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== References ==

[[Category: Qin, J]]

[[Category: Zhu, L]]

[[Category: Zinc finger]]