4lnp

From Proteopedia

(Difference between revisions)

Revision as of 09:50, 3 April 2019

The first SH3 domain from CAP/Ponsin in complex with proline rich peptide from Vinculin

Structural highlights

4lnp is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4ln2, 2mox
Gene:	KIAA0894, KIAA1296, SH3D5, SORBS1 (HUMAN), VCL (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[VINC_HUMAN] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM: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.^[1] ^[2] Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM: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.^[3]

Function

[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] [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.^[4]

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^[5]

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

References

↑ Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002 Jan 29;105(4):431-7. PMID:11815424
↑ Vasile VC, Will ML, Ommen SR, Edwards WD, Olson TM, Ackerman MJ. Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy. Mol Genet Metab. 2006 Feb;87(2):169-74. Epub 2005 Oct 19. PMID:16236538 doi:S1096-7192(05)00258-1
↑ Vasile VC, Ommen SR, Edwards WD, Ackerman MJ. A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Jul 7;345(3):998-1003. Epub 2006 May 4. PMID:16712796 doi:S0006-291X(06)00981-8
↑ Le Clainche C, Dwivedi SP, Didry D, Carlier MF. Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein. J Biol Chem. 2010 Jul 23;285(30):23420-32. doi: 10.1074/jbc.M110.102830. Epub, 2010 May 18. PMID:20484056 doi:10.1074/jbc.M110.102830
↑ 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. Structural investigation of the interaction between the tandem SH3 domains of c-Cbl-associated protein and vinculin. J Struct Biol. 2014 Aug;187(2):194-205. doi: 10.1016/j.jsb.2014.05.009. Epub 2014, May 28. PMID:24878663 doi:http://dx.doi.org/10.1016/j.jsb.2014.05.009

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lnp"

@@ Line 1: / Line 1: @@
 ==The first SH3 domain from CAP/Ponsin in complex with proline rich peptide from Vinculin==
-<StructureSection load='4lnp' size='340' side='right' caption='[[4lnp]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
+<StructureSection load='4lnp' size='340' side='right'caption='[[4lnp]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4lnp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LNP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4lnp]] is a 2 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=4LNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LNP FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ln2|4ln2]], [[2mox|2mox]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0894, KIAA1296, SH3D5, SORBS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VCL ([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=4lnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lnp OCA], [http://pdbe.org/4lnp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lnp RCSB], [http://www.ebi.ac.uk/pdbsum/4lnp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lnp ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gong, Q]]
 [[Category: Li, F]]

4lnp

From Proteopedia

Revision as of 09:50, 3 April 2019

The first SH3 domain from CAP/Ponsin in complex with proline rich peptide from Vinculin

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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