5o2q

From Proteopedia

(Difference between revisions)

Current revision

p130Cas SH3 domain Vinculin peptide chimera

Structural highlights

5o2q is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
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

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] BCAR1_HUMAN Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.^[5] ^[6]

Publication Abstract from PubMed

CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.

Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.,Gemperle J, Hexnerova R, Lepsik M, Tesina P, Dibus M, Novotny M, Brabek J, Veverka V, Rosel D Sci Rep. 2017 Aug 14;7(1):8057. doi: 10.1038/s41598-017-08303-4. PMID:28808245^[7]

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
↑ Abassi YA, Rehn M, Ekman N, Alitalo K, Vuori K. p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J Biol Chem. 2003 Sep 12;278(37):35636-43. Epub 2003 Jun 28. PMID:12832404 doi:http://dx.doi.org/10.1074/jbc.M306438200
↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
↑ Gemperle J, Hexnerova R, Lepsik M, Tesina P, Dibus M, Novotny M, Brabek J, Veverka V, Rosel D. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners. Sci Rep. 2017 Aug 14;7(1):8057. doi: 10.1038/s41598-017-08303-4. PMID:28808245 doi:http://dx.doi.org/10.1038/s41598-017-08303-4

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/5o2q"

Categories: Homo sapiens | Large Structures | Hexnerova R | Veverka V

@@ Line 1: / Line 1: @@
 ==p130Cas SH3 domain Vinculin peptide chimera==
-<StructureSection load='5o2q' size='340' side='right' caption='[[5o2q]], [[NMR_Ensembles_of_Models | 40 NMR models]]' scene=''>
+<StructureSection load='5o2q' size='340' side='right'caption='[[5o2q]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o2q]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O2Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O2Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o2q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O2Q 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=5o2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o2q OCA], [http://pdbe.org/5o2q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o2q RCSB], [http://www.ebi.ac.uk/pdbsum/5o2q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o2q ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=5o2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o2q OCA], [https://pdbe.org/5o2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o2q RCSB], [https://www.ebi.ac.uk/pdbsum/5o2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o2q ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:[https://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:[https://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 ==
+[https://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/BCAR1_HUMAN BCAR1_HUMAN] Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.<ref>PMID:12832404</ref> <ref>PMID:17038317</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Hexnerova, R]]
+[[Category: Homo sapiens]]
-[[Category: Veverka, V]]
+[[Category: Large Structures]]
-[[Category: P130ca]]
+[[Category: Hexnerova R]]
-[[Category: Sh3 domain]]
+[[Category: Veverka V]]
-[[Category: Structure from cyana 3 97]]

5o2q

From Proteopedia

Current revision

p130Cas SH3 domain Vinculin peptide chimera

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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