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PDBsum entry 2vrw
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protein metals Protein-protein interface(s) links
Signaling protein PDB id
2vrw

 

 

 

 

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Contents
Protein chains
177 a.a. *
367 a.a. *
Metals
_ZN ×2
Waters ×471
* Residue conservation analysis
PDB id:
2vrw
Name: Signaling protein
Title: Critical structural role for the ph and c1 domains of the vav1 exchange factor
Structure: Ras-related c3 botulinum toxin substrate 1. Chain: a. Fragment: residues 1-184. Synonym: p21-rac1, ras- like protein tc25, cell migration-inducing gene 5 protein, rac1. Engineered: yes. Proto-oncogene vav. Chain: b. Fragment: residues 170-575.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Mus musculus. Mouse. Organism_taxid: 10090.
Resolution:
1.85Å     R-factor:   0.205     R-free:   0.251
Authors: J.Rapley,V.Tybulewicz,K.Rittinger
Key ref: J.Rapley et al. (2008). Crucial structural role for the PH and C1 domains of the Vav1 exchange factor. Embo Rep, 9, 655-661. PubMed id: 18511940 DOI: 10.1038/embor.2008.80
Date:
16-Apr-08     Release date:   17-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63000  (RAC1_HUMAN) -  Ras-related C3 botulinum toxin substrate 1 from Homo sapiens
Seq:
Struc: 		192 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
P27870  (VAV_MOUSE) -  Proto-oncogene vav from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		845 a.a.
367 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.3.6.5.2  - small monomeric GTPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: GTP + H2O = GDP + phosphate + H+
GTP
 + H2O
 = GDP
 + phosphate
 + H(+)
   Enzyme class 2: Chain B: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/embor.2008.80 Embo Rep 9:655-661 (2008)
PubMed id: 18511940  
 
 
Crucial structural role for the PH and C1 domains of the Vav1 exchange factor.
J.Rapley, V.L.Tybulewicz, K.Rittinger.
 
  ABSTRACT  
 
The Vav family of proteins are guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases, which regulate various cellular functions, including T-cell activation. They contain a catalytic Dbl homology (DH) domain that is invariably followed by a pleckstrin homology (PH) domain, which is often required for catalytic activity. Vav proteins are the first GEFs for which an additional C1 domain is required for full biological activity. Here, we present the structure of a Vav1 fragment comprising the DH-PH-C1 domains bound to Rac1. This structure shows that the PH and C1 domains form a single structural unit that packs against the carboxy-terminal helix of the DH domain to stabilize its conformation and to promote nucleotide exchange. In contrast to previous reports, this structure shows that there are no direct contacts between the GTPase and C1 domain but instead suggests new mechanisms for the regulation of Vav1 activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20141838 B.Yu, I.R.Martins, P.Li, G.K.Amarasinghe, J.Umetani, M.E.Fernandez-Zapico, D.D.Billadeau, M.Machius, D.R.Tomchick, and M.K.Rosen (2010).
Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1.
  Cell, 140, 246-256.
PDB code: 3ky9
19951033 S.Rosales-Corral, R.J.Reiter, D.X.Tan, G.G.Ortiz, and G.Lopez-Armas (2010).
Functional aspects of redox control during neuroinflammation.
  Antioxid Redox Signal, 13, 193-247.  
19100858 S.Katzav (2009).
Vav1: a hematopoietic signal transduction molecule involved in human malignancies.
  Int J Biochem Cell Biol, 41, 1245-1248.  
19670212 T.Cierpicki, J.Bielnicki, M.Zheng, J.Gruszczyk, M.Kasterka, M.Petoukhov, A.Zhang, E.J.Fernandez, D.I.Svergun, U.Derewenda, J.H.Bushweller, and Z.S.Derewenda (2009).
The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA.
  Protein Sci, 18, 2067-2079.  
19909369 T.T.Zhang, H.Li, S.M.Cheung, J.L.Costantini, S.Hou, M.Al-Alwan, and A.J.Marshall (2009).
Phosphoinositide 3-kinase-regulated adapters in lymphocyte activation.
  Immunol Rev, 232, 255-272.  
18974134 C.Ambrogio, C.Voena, A.D.Manazza, C.Martinengo, C.Costa, T.Kirchhausen, E.Hirsch, G.Inghirami, and R.Chiarle (2008).
The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation.
  Cancer Res, 68, 8899-8907.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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