PDBsum entry: 1f5x

Signaling protein

PDB id: 1f5x

Contents

Protein chain

208 a.a. *

* Residue conservation analysis

PDB id:

1f5x

Name:

Signaling protein

Title:

Nmr structure of the y174 autoinhibited dbl homology domain

Structure:

Rho-gef vav. Chain: a. Fragment: dbl homology domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

B.Aghazadeh,M.K.Rosen,W.E.Lowry,X.Y.Huang

Key ref:

B.Aghazadeh et al. (2000). Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation. Cell, 102, 625-633. PubMed id: 11007481 DOI: 10.1016/S0092-8674(00)00085-4

Date:

18-Jun-00 Release date: 15-Sep-00

Protein chain

P27870  (VAV_MOUSE) -  Proto-oncogene vav

Seq: 845 a.a.

Struc: 208 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: regulation of Rho protein signal transduction (1 term)
• Biochemical function: guanyl-nucleotide exchange factor activity (2 terms)

DOI no: 10.1016/S0092-8674(00)00085-4

Cell 102:625-633 (2000)

PubMed id: 11007481

Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation.

B.Aghazadeh, W.E.Lowry, X.Y.Huang, M.K.Rosen.

ABSTRACT

Rho-family GTPases transduce signals from receptors leading to changes in cell shape and motility, mitogenesis, and development. Proteins containing the Dbl homology (DH) domain are responsible for activating Rho GTPases by catalyzing the exchange of GDP for GTP. Receptor-initiated stimulation of Dbl protein Vav exchange activity involves tyrosine phosphorylation. We show through structure determination that the mVav1 DH domain is autoinhibited by an N-terminal extension, which lies in the GTPase interaction site. This extension contains the Tyr174 Src-family kinase recognition site, and phosphorylation or truncation of this peptide results in stimulation of GEF activity. NMR spectroscopy data show that the N-terminal peptide is released from the DH domain and becomes unstructured upon phosphorylation. Thus, tyrosine phosphorylation relieves autoinhibition by exposing the GTPase interaction surface of the DH domain, which is obligatory for Vav activation.

Selected figure(s)

Figure 3.
Figure 3. Structure of the Autoinhibited Vav170–375(A) Ribbons ([12]) depiction of a representative confomer from the final ensemble of Vav DH domain structures. Residues 170–180 encompassing the inhibitory helix are red, 181–375 are yellow, loops are green.(B) Autoinhibited DH domain, rotated vert, similar 90° about a vertical axis with respect to 3A. Left: a yellow molecular surface of the DH domain (residues 195–375) with the N-terminal autoinhibitory arm (residues 170–194) depicted as a red ribbon. Right: indicated expansion of the binding site of the inhibitory helix on the DH domain. Residues involved in the interaction are colored green on the DH domain and red on the inhibitory helix. Molecular surfaces of the DH domain represented as a yellow net. Figure produced with GRASP ([45]).

Figure 5.
Figure 5. Model of Vav DH Domain Autoinhibition by Tyr174 Src Recognition Motif and PH Domain

The above figures are reprinted by permission from Cell Press: Cell (2000, 102, 625-633) copyright 2000.

Figures were selected by an automated process.