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5xq1

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Revision as of 06:56, 14 October 2020

Structural basis of kindlin-mediated integrin recognition and activation

Structural highlights

5xq1 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FERM2_MOUSE] 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]

Publication Abstract from PubMed

Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain-containing proteins, talins and kindlins, respectively, bind different regions of beta-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the beta1- and beta3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.

Structural basis of kindlin-mediated integrin recognition and activation.,Li H, Deng Y, Sun K, Yang H, Liu J, Wang M, Zhang Z, Lin J, Wu C, Wei Z, Yu C Proc Natl Acad Sci U S A. 2017 Jul 24. pii: 201703064. doi:, 10.1073/pnas.1703064114. PMID:28739949^[4]

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

References

↑ Dowling JJ, Gibbs E, Russell M, Goldman D, Minarcik J, Golden JA, Feldman EL. Kindlin-2 is an essential component of intercalated discs and is required for vertebrate cardiac structure and function. Circ Res. 2008 Feb 29;102(4):423-31. doi: 10.1161/CIRCRESAHA.107.161489. Epub, 2008 Jan 3. PMID:18174465 doi:http://dx.doi.org/10.1161/CIRCRESAHA.107.161489
↑ Montanez E, Ussar S, Schifferer M, Bosl M, Zent R, Moser M, Fassler R. Kindlin-2 controls bidirectional signaling of integrins. Genes Dev. 2008 May 15;22(10):1325-30. doi: 10.1101/gad.469408. PMID:18483218 doi:http://dx.doi.org/10.1101/gad.469408
↑ Pluskota E, Dowling JJ, Gordon N, Golden JA, Szpak D, West XZ, Nestor C, Ma YQ, Bialkowska K, Byzova T, Plow EF. The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish. Blood. 2011 May 5;117(18):4978-87. doi: 10.1182/blood-2010-11-321182. Epub 2011, Mar 4. PMID:21378273 doi:http://dx.doi.org/10.1182/blood-2010-11-321182
↑ Li H, Deng Y, Sun K, Yang H, Liu J, Wang M, Zhang Z, Lin J, Wu C, Wei Z, Yu C. Structural basis of kindlin-mediated integrin recognition and activation. Proc Natl Acad Sci U S A. 2017 Jul 24. pii: 201703064. doi:, 10.1073/pnas.1703064114. PMID:28739949 doi:http://dx.doi.org/10.1073/pnas.1703064114

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/5xq1"

@@ Line 1: / Line 1: @@
 ==Structural basis of kindlin-mediated integrin recognition and activation==
-<StructureSection load='5xq1' size='340' side='right' caption='[[5xq1]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
+<StructureSection load='5xq1' size='340' side='right'caption='[[5xq1]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xq1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XQ1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xq1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQ1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XQ1 FirstGlance]. <br>
-</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=5xq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xq1 OCA], [http://pdbe.org/5xq1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xq1 RCSB], [http://www.ebi.ac.uk/pdbsum/5xq1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xq1 ProSAT]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xq1 OCA], [http://pdbe.org/5xq1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xq1 RCSB], [http://www.ebi.ac.uk/pdbsum/5xq1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xq1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 21: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Li, H]]
 [[Category: Sun, K]]

5xq1

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Revision as of 06:56, 14 October 2020

Structural basis of kindlin-mediated integrin recognition and activation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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