2lgx

From Proteopedia

(Difference between revisions)

Revision as of 23:08, 11 September 2015

NMR structure for Kindle-2 N-terminus

Structural highlights

2lgx is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	FERMT2, KIND2, MIG2, PLEKHC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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]

Publication Abstract from PubMed

Kindlin-2 belongs to an emerging class of regulators for heterodimeric (alpha/beta) integrin adhesion receptors. By binding to integrin beta cytoplasmic tail via its C-terminal FERM-like domain, kindlin-2 promotes integrin activation. Intriguingly, this activation process depends on the N terminus of kindlin-2 (K2-N) that precedes the FERM domain. The molecular function of K2-N is unclear. We present the solution structure of K2-N, which displays a ubiquitin fold similar to that observed in kindlin-1. Using chemical shift mapping and mutagenesis, we found that K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate. We show that while wild-type kindlin-2 is capable of promoting integrin activation, such ability is significantly reduced for its membrane-binding defective mutant. These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation.

Membrane Binding of the N-Terminal Ubiquitin-Like Domain of kindlin-2 Is Crucial for Its Regulation of Integrin Activation.,Perera HD, Ma YQ, Yang J, Hirbawi J, Plow EF, Qin J Structure. 2011 Nov 9;19(11):1664-71. PMID:22078565^[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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lgx"

@@ Line 2: / Line 2: @@
 <StructureSection load='2lgx' size='340' side='right' caption='[[2lgx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2lgx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LGX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2lgx]] is a 1 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=2LGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LGX FirstGlance]. <br>
-</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 Homo sapiens])</td></tr>
+</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])</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=2lgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lgx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lgx RCSB], [http://www.ebi.ac.uk/pdbsum/2lgx PDBsum]</span></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=2lgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lgx OCA], [http://pdbe.org/2lgx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lgx RCSB], [http://www.ebi.ac.uk/pdbsum/2lgx PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2lgx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Hirbawi, J]]
 [[Category: Ma, Y]]

2lgx

From Proteopedia

Revision as of 23:08, 11 September 2015

NMR structure for Kindle-2 N-terminus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox