2lnw

From Proteopedia

(Difference between revisions)

Revision as of 14:54, 25 December 2014

Identification and structural basis for a novel interaction between Vav2 and Arap3

Structural highlights

2lnw is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	2lnx
Gene:	VAV2 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[VAV2_HUMAN] Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). [ARAP3_HUMAN] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.^[1] ^[2]

Publication Abstract from PubMed

Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. It regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins. In this study, Arap3, a dual GTPase-activating protein (GAP) for RhoA and Arf6, was first identified to be a novel interaction partner for Vav2 both in vitro and in vivo. ITC and NMR chemical shift perturbation experiments demonstrated that Vav2 SH2 domain was able to interact directly with phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 with high affinities, with the dissociation constants (Kd) of approximately 0.27 and approximately 1.40muM, respectively. In addition, using different phosphotyrosine peptides, the pY +3 specificity of Vav2 SH2 domain was discovered. The solution structures of Vav2 SH2 domain in free and in complex with the phosphotyrosine peptide pY1408 were therefore determined to understand the structural basis of this recognition specificity. Structural analysis revealed that the presence of a Phe residue in the BG loop (BG6) leads to the formation of a shallow hydrophobic pY +3 pocket on the surface of Vav2 SH2 domain, which determines the pY +3 specificity of Vav2 SH2 domain.

Identification and structural basis for a novel interaction between Vav2 and Arap3.,Wu B, Wang F, Zhang J, Zhang Z, Qin L, Peng J, Li F, Liu J, Lu G, Gong Q, Yao X, Wu J, Shi Y J Struct Biol. 2012 Oct;180(1):84-95. doi: 10.1016/j.jsb.2012.06.011. Epub 2012, Jun 28. PMID:22750419^[3]

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

References

↑ Krugmann S, Anderson KE, Ridley SH, Risso N, McGregor A, Coadwell J, Davidson K, Eguinoa A, Ellson CD, Lipp P, Manifava M, Ktistakis N, Painter G, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Dove SK, Michell RH, Grewal A, Nazarian A, Erdjument-Bromage H, Tempst P, Stephens LR, Hawkins PT. Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol Cell. 2002 Jan;9(1):95-108. PMID:11804589
↑ Lu Q, Wei W, Kowalski PE, Chang AC, Cohen SN. EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17246-51. Epub 2004 Nov 29. PMID:15569923 doi:http://dx.doi.org/10.1073/pnas.0407794101
↑ Wu B, Wang F, Zhang J, Zhang Z, Qin L, Peng J, Li F, Liu J, Lu G, Gong Q, Yao X, Wu J, Shi Y. Identification and structural basis for a novel interaction between Vav2 and Arap3. J Struct Biol. 2012 Oct;180(1):84-95. doi: 10.1016/j.jsb.2012.06.011. Epub 2012, Jun 28. PMID:22750419 doi:http://dx.doi.org/10.1016/j.jsb.2012.06.011

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lnw"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2lnw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LNW FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lnx|2lnx]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lnx|2lnx]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VAV2 ([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">VAV2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2lnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lnw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lnw RCSB], [http://www.ebi.ac.uk/pdbsum/2lnw 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=2lnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lnw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lnw RCSB], [http://www.ebi.ac.uk/pdbsum/2lnw PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/VAV2_HUMAN VAV2_HUMAN]] Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). [[http://www.uniprot.org/uniprot/ARAP3_HUMAN ARAP3_HUMAN]] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.<ref>PMID:11804589</ref> <ref>PMID:15569923</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Shi, Y.]]
+[[Category: Shi, Y]]
-[[Category: Wu, B.]]
+[[Category: Wu, B]]
-[[Category: Wu, J.]]
+[[Category: Wu, J]]
-[[Category: Zhang, J.]]
+[[Category: Zhang, J]]
 [[Category: Signaling protein]]

2lnw

From Proteopedia

Revision as of 14:54, 25 December 2014

Identification and structural basis for a novel interaction between Vav2 and Arap3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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