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3rqf

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Revision as of 15:17, 11 August 2016

Cerebral cavernous malformation 3 (CCM3) in complex with paxillin LD2

Structural highlights

3rqf is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3l8i, 3l8j, 3ajm, 3rqe, 3rqg
Gene:	PDCD10, CCM3, TFAR15 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PDC10_HUMAN] Hereditary cerebral cavernous malformation. Defects in PDCD10 are the cause of cerebral cavernous malformations type 3 (CCM3) [MIM:603285]. Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. CCMs have an incidence of 0.1%-0.5% in the general population and usually present clinically during the 3rd to 5th decade of life. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters.^[1]

Function

[PDC10_HUMAN] Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and MST4 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development (By similarity).^[2] ^[3] ^[4]

Publication Abstract from PubMed

Cerebral cavernous malformation (CCM) is a disease that affects between 0.1 and 0.5% of the human population, with mutations in CCM3 accounting for approximately 15% of the autosomal dominant form of the disease. We recently reported that CCM3 contains an N-terminal dimerization domain (CCM3D) and a C-terminal focal adhesion targeting (FAT)-homology domain. Intermolecular protein-protein interactions of CCM3 are mediated by a highly conserved surface on the FAT-homology domain and are affected by CCM3 truncations in the human disease. Here we report the crystal structures of CCM3 in complex with three different leucine-aspartate repeat (LD) motifs (LD1, LD2 and LD4) from the scaffolding protein paxillin, at 2.8 A, 2.7 A and 2.5 A resolution. We show that CCM3 binds LD motifs using the highly conserved Hydrophobic Patch 1 (HP1) and that this binding is similar to the binding of FAK and Pyk2 FAT domains to paxillin LD motifs. We further show by Surface Plasmon Resonance that CCM3 binds paxillin LD motifs with affinities in the micromolar range, similar to FAK family FAT domains. Finally, we show that endogenous CCM3 and paxillin co-localize in mouse cerebral pericytes. These studies provide a molecular-level framework to investigate the protein-protein interactions of CCM3.

Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting-homology domain of cerebral cavernous malformation 3 (CCM3).,Li X, Ji W, Zhang R, Folta-Stogniew E, Min W, Boggon TJ J Biol Chem. 2011 Jun 1. PMID:21632544^[5]

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

References

↑ Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet. 2005 Jan;76(1):42-51. Epub 2004 Nov 12. PMID:15543491 doi:10.1086/426952
↑ Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet. 2005 Jan;76(1):42-51. Epub 2004 Nov 12. PMID:15543491 doi:10.1086/426952
↑ Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D. PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell. 2007 Jun;18(6):1965-78. Epub 2007 Mar 14. PMID:17360971 doi:10.1091/mbc.E06-07-0608
↑ Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J. CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation. J Cell Sci. 2010 Apr 15;123(Pt 8):1274-84. doi: 10.1242/jcs.061341. Epub 2010 Mar, 23. PMID:20332113 doi:10.1242/jcs.061341
↑ Li X, Ji W, Zhang R, Folta-Stogniew E, Min W, Boggon TJ. Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting-homology domain of cerebral cavernous malformation 3 (CCM3). J Biol Chem. 2011 Jun 1. PMID:21632544 doi:10.1074/jbc.M110.211250

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3rqf"

@@ Line 1: / Line 1: @@
 ==Cerebral cavernous malformation 3 (CCM3) in complex with paxillin LD2==
 <StructureSection load='3rqf' size='340' side='right' caption='[[3rqf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rqf]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RQF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rqf]] is a 5 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=3RQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RQF FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l8i|3l8i]], [[3l8j|3l8j]], [[3ajm|3ajm]], [[3rqe|3rqe]], [[3rqg|3rqg]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD10, CCM3, TFAR15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD10, CCM3, TFAR15 ([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=3rqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rqf RCSB], [http://www.ebi.ac.uk/pdbsum/3rqf PDBsum]</span></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=3rqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqf OCA], [http://pdbe.org/3rqf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rqf RCSB], [http://www.ebi.ac.uk/pdbsum/3rqf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rqf ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3rqf" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Cell death protein|Cell death protein]]
+*[[Paxillin|Paxillin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Boggon, T J]]
 [[Category: Li, X]]

3rqf

From Proteopedia

Revision as of 15:17, 11 August 2016

Cerebral cavernous malformation 3 (CCM3) in complex with paxillin LD2

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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