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==The second SH3 domain from CAP/Ponsin in complex with proline rich peptide from Vinculin==
==The second SH3 domain from CAP/Ponsin in complex with proline rich peptide from Vinculin==
<StructureSection load='4ln2' size='340' side='right' caption='[[4ln2]], [[Resolution|resolution]] 1.00&Aring;' scene=''>
<StructureSection load='4ln2' size='340' side='right'caption='[[4ln2]], [[Resolution|resolution]] 1.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ln2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LN2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ln2]] 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=4LN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LN2 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lnp|4lnp]], [[2mox|2mox]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1&#8491;</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ln2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ln2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ln2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ln2 PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ln2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ln2 OCA], [https://pdbe.org/4ln2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ln2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ln2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ln2 ProSAT]</span></td></tr>
<table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN]] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:[http://omim.org/entry/611407 611407]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:11815424</ref> <ref>PMID:16236538</ref>   Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM:[http://omim.org/entry/613255 613255]]. It is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:16712796</ref>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SRBS1_HUMAN SRBS1_HUMAN]] Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity).[UniProtKB:Q62417] [[http://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN]] Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.<ref>PMID:20484056</ref>
[https://www.uniprot.org/uniprot/SRBS1_HUMAN SRBS1_HUMAN] Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity).[UniProtKB:Q62417]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
c-Cbl-associated protein (CAP) is an important cytoskeletal adaptor protein involved in the regulation of adhesion turnover. The interaction between CAP and vinculin is critical for the recruitment of CAP to focal adhesions. The tandem SH3 domains (herein termed SH3a and SH3b) of CAP are responsible for its interaction with vinculin. However, the structural mechanism underlying the interaction between CAP and vinculin is poorly understood. In this manuscript, we report the solution structure of the tandem SH3 domains of CAP. Our NMR and ITC data indicate that the SH3a and SH3b domains of CAP simultaneously bind to a long proline-rich region of vinculin with different binding specificities. Furthermore, the crystal structures of the individual SH3a and SH3b domains complexed with their substrate peptides indicate that Q807(SH3a) and D881(SH3b) are the critical residues determining the different binding specificities of the SH3 domains. Based on the obtained structural information, a model of the SH3ab-vinculin complex was generated using MD simulation and SAXS data.
 
Structural investigation of the interaction between the tandem SH3 domains of c-Cbl-associated protein and vinculin.,Zhao D, Wang X, Peng J, Wang C, Li F, Sun Q, Zhang Y, Zhang J, Cai G, Zuo X, Wu J, Shi Y, Zhang Z, Gong Q J Struct Biol. 2014 Aug;187(2):194-205. doi: 10.1016/j.jsb.2014.05.009. Epub 2014, May 28. PMID:24878663<ref>PMID:24878663</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ln2" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Gong, Q.]]
[[Category: Homo sapiens]]
[[Category: Li, F.]]
[[Category: Large Structures]]
[[Category: Shi, Y.]]
[[Category: Gong Q]]
[[Category: Wu, J.]]
[[Category: Li F]]
[[Category: Zhang, Z.]]
[[Category: Shi Y]]
[[Category: Zhao, D.]]
[[Category: Wu J]]
[[Category: Cell migration]]
[[Category: Zhang Z]]
[[Category: Focal adhesion]]
[[Category: Zhao D]]
[[Category: Sh3 domain]]
[[Category: Signaling protein]]

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