This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6u4n

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 18:00, 20 November 2019

Solution structure of paxillin LIM4 in complex with kindlin-2 F0

Structural highlights

6u4n is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6u4m
Gene:	FERMT2, KIND2, MIG2, PLEKHC1 (HUMAN), PXN (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [PAXI_HUMAN] Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion).

Publication Abstract from PubMed

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.

Structural Basis of Paxillin Recruitment by Kindlin-2 in Regulating Cell Adhesion.,Zhu L, Liu H, Lu F, Yang J, Byzova TV, Qin J Structure. 2019 Sep 30. pii: S0969-2126(19)30312-0. doi:, 10.1016/j.str.2019.09.006. PMID:31590942^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tu Y, Wu S, Shi X, Chen K, Wu C. Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell. 2003 Apr 4;113(1):37-47. PMID:12679033
↑ Ma YQ, Qin J, Wu C, Plow EF. Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J Cell Biol. 2008 May 5;181(3):439-46. doi: 10.1083/jcb.200710196. PMID:18458155 doi:http://dx.doi.org/10.1083/jcb.200710196
↑ Qu H, Tu Y, Shi X, Larjava H, Saleem MA, Shattil SJ, Fukuda K, Qin J, Kretzler M, Wu C. Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins. J Cell Sci. 2011 Mar 15;124(Pt 6):879-91. doi: 10.1242/jcs.076976. Epub 2011 Feb , 15. PMID:21325030 doi:http://dx.doi.org/10.1242/jcs.076976
↑ Yu Y, Wu J, Wang Y, Zhao T, Ma B, Liu Y, Fang W, Zhu WG, Zhang H. Kindlin 2 forms a transcriptional complex with beta-catenin and TCF4 to enhance Wnt signalling. EMBO Rep. 2012 Aug;13(8):750-8. doi: 10.1038/embor.2012.88. Epub 2012 Jun 15. PMID:22699938 doi:http://dx.doi.org/10.1038/embor.2012.88
↑ Liu J, Fukuda K, Xu Z, Ma YQ, Hirbawi J, Mao X, Wu C, Plow EF, Qin J. Structural basis of phosphoinositide binding to kindlin-2 protein pleckstrin homology domain in regulating integrin activation. J Biol Chem. 2011 Dec 16;286(50):43334-42. Epub 2011 Oct 26. PMID:22030399 doi:10.1074/jbc.M111.295352
↑ Perera HD, Ma YQ, Yang J, Hirbawi J, Plow EF, Qin J. Membrane Binding of the N-Terminal Ubiquitin-Like Domain of kindlin-2 Is Crucial for Its Regulation of Integrin Activation. Structure. 2011 Nov 9;19(11):1664-71. PMID:22078565 doi:10.1016/j.str.2011.08.012
↑ Zhu L, Liu H, Lu F, Yang J, Byzova TV, Qin J. Structural Basis of Paxillin Recruitment by Kindlin-2 in Regulating Cell Adhesion. Structure. 2019 Sep 30. pii: S0969-2126(19)30312-0. doi:, 10.1016/j.str.2019.09.006. PMID:31590942 doi:http://dx.doi.org/10.1016/j.str.2019.09.006

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6u4n"

@@ Line 3: / Line 3: @@
 <StructureSection load='6u4n' size='340' side='right'caption='[[6u4n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[6u4n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FERMT2, KIND2, MIG2, PLEKHC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PXN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
 </table>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 6u4n" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Paxillin|Paxillin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Qin, J]]

6u4n

From Proteopedia

Revision as of 18:00, 20 November 2019

Solution structure of paxillin LIM4 in complex with kindlin-2 F0

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox