4f7h

From Proteopedia

(Difference between revisions)

Revision as of 08:07, 11 August 2016

The crystal structure of kindlin-2 pleckstrin homology domain in free form

Structural highlights

4f7h is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2lko
Gene:	FERMT2, KIND2, MIG2, PLEKHC1 (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]

Publication Abstract from PubMed

Kindlin-2 belongs to a subfamily of FERM domain containing proteins, which plays key roles in activating integrin transmembrane receptors and mediating cell adhesion. Compared to conventional FERM domains, kindlin-2 FERM contains an inserted pleckstrin homology (PH) domain that specifically binds to phosphatidylinositol (3,4,5) trisphosphate (PIP3) and regulates the kindlin-2 function. We have determined the crystal structure of kindlin-2 PH domain at 1.9 A resolution, which reveals a conserved PH domain fold with a highly charged and open binding pocket for PIP3 head group. Structural comparison with a previously reported solution structure of kindlin-2 PH domain bound to PIP3 head group reveals that upon PIP3 insertion, there is a significant conformational change of both the highly positively charged loop at the entry of the PIP3 binding pocket and the entire beta barrel of the PH domain. We propose that such "induced-fit" type change is crucial for the tight binding of PIP3 to anchor kindlin-2 onto the membrane surface, thereby promoting its binding to integrins. Our results provide important structural insight into kindlin-2-mediated membrane anchoring and integrin activation.

Crystal structure of kindlin-2 PH domain reveals a conformational transition for its membrane anchoring and regulation of integrin activation.,Liu Y, Zhu Y, Ye S, Zhang R Protein Cell. 2012 May 31. PMID:22653426^[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
↑ Liu Y, Zhu Y, Ye S, Zhang R. Crystal structure of kindlin-2 PH domain reveals a conformational transition for its membrane anchoring and regulation of integrin activation. Protein Cell. 2012 May 31. PMID:22653426 doi:10.1007/s13238-012-2046-1

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/4f7h"

@@ Line 1: / Line 1: @@
 ==The crystal structure of kindlin-2 pleckstrin homology domain in free form==
 <StructureSection load='4f7h' size='340' side='right' caption='[[4f7h]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f7h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F7H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f7h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F7H FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SRT:S,R+MESO-TARTARIC+ACID'>SRT</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lko|2lko]]</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>
+<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=4f7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f7h RCSB], [http://www.ebi.ac.uk/pdbsum/4f7h 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=4f7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7h OCA], [http://pdbe.org/4f7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f7h RCSB], [http://www.ebi.ac.uk/pdbsum/4f7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7h ProSAT]</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 16: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f7h" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Liu, Y]]
 [[Category: Qin, J]]

4f7h

From Proteopedia

Revision as of 08:07, 11 August 2016

The crystal structure of kindlin-2 pleckstrin homology domain in free form

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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