6v97

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==Kindlin-3 double deletion mutant short form==
==Kindlin-3 double deletion mutant short form==
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<StructureSection load='6v97' size='340' side='right'caption='[[6v97]]' scene=''>
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<StructureSection load='6v97' size='340' side='right'caption='[[6v97]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V97 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V97 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6v97]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V97 FirstGlance]. <br>
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</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=6v97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v97 OCA], [http://pdbe.org/6v97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v97 RCSB], [http://www.ebi.ac.uk/pdbsum/6v97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v97 ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.381&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6v97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v97 OCA], [https://pdbe.org/6v97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v97 RCSB], [https://www.ebi.ac.uk/pdbsum/6v97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v97 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/URP2_HUMAN URP2_HUMAN] Leukocyte adhesion deficiency type III. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref> <ref>PMID:18779414</ref> <ref>PMID:19617577</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/URP2_HUMAN URP2_HUMAN] Plays a central role in cell adhesion in hematopoietic cells. Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells. Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity).<ref>PMID:18280249</ref> <ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref> Isoform 2 may act as a repressor of NF-kappa-B and apoptosis.<ref>PMID:18280249</ref> <ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Kindlin-3, a protein 4.1, ezrin, radixin, and moesin (FERM) domain-containing adaptor in hematopoietic cells, is essentially required for supporting the bidirectional integrin alphaIIbbeta3 signaling in platelets by binding to the integrin beta3 cytoplasmic tail. However, the structural details of kindlin-3's FERM domain remain unknown. In this study, we crystalized the kindlin-3's FERM domain protein and successfully solved its 3-dimensional structure. The structure shows that the 3 kindlin-3's FERM subdomains (F1, F2, and F3) compact together and form a cloverleaf-shaped conformation, which is stabilized by the binding interface between the F1 and F3 subdomains. Interestingly, the FERM domain of kindlin-3 exists as a monomer in both crystal and solution, which is different from its counterpart in kindlin-2 that is able to form a F2 subdomain-swapped dimer; nonetheless, dimerization is required for kindlin-3 to support integrin alphaIIbbeta3 activation, indicating that kindlin-3 may use alternative mechanisms for formation of a functional dimer in cells. To evaluate the functional importance of the cloverleaf-like FERM structure in kindlin-3, structure-based mutations were introduced into kindlin-3 to disrupt the F1/F3 interface. The results show that integrin alphaIIbbeta3 activation is significantly suppressed in platelets expressing the kindlin-3 mutant compared with those expressing wild-type kindlin-3. In addition, introduction of equivalent mutations into kindlin-1 and kindlin-2 also significantly compromises their ability to support integrin alphaIIbbeta3 activation in CHO cells. Together, our findings suggest that the cloverleaf-like FERM domain in kindlins is structurally important for supporting integrin alphaIIbbeta3 activation.
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Structure basis of the FERM domain of kindlin-3 in supporting integrin alphaIIbbeta3 activation in platelets.,Sun J, Xiao D, Ni Y, Zhang T, Cao Z, Xu Z, Nguyen H, Zhang J, White GC, Ding J, Ma YQ, Xu Z Blood Adv. 2020 Jul 14;4(13):3128-3135. doi: 10.1182/bloodadvances.2020001575. PMID:32649767<ref>PMID:32649767</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6v97" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ding JP]]
[[Category: Ding JP]]

Current revision

Kindlin-3 double deletion mutant short form

PDB ID 6v97

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