PDBsum entry 3ky9

Apoptosis

PDB id

3ky9

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Contents

			Protein chains

					530 a.a. *

			Metals

					_ZN ×4

* Residue conservation analysis

PDB id:

3ky9

Links

Name:

Apoptosis

Title:

Autoinhibited vav1

Structure:

Proto-oncogene vav. Chain: a, b. Fragment: ch-dh-ph-c1 domains. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: vav, vav1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.73Å

R-factor:

0.225

R-free:

0.271

Authors:

D.R.Tomchick,M.K.Rosen,M.Machius,B.Yu

Key ref:

B.Yu et al. (2010). Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Cell, 140, 246-256. PubMed id: 20141838

Date:

04-Dec-09

Release date:

23-Feb-10

PROCHECK

	Headers

	References

Protein chains

P15498 (VAV_HUMAN) - Proto-oncogene vav from Homo sapiens

Seq: Struc:

Seq: Struc:					845 a.a. 530 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

	Cell 140:246-256 (2010)
PubMed id: 20141838

Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1.
B.Yu, I.R.Martins, P.Li, G.K.Amarasinghe, J.Umetani, M.E.Fernandez-Zapico, D.D.Billadeau, M.Machius, D.R.Tomchick, M.K.Rosen.

ABSTRACT

Vav proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. They control processes including T cell activation, phagocytosis, and migration of normal and transformed cells. We report the structure and biophysical and cellular analyses of the five-domain autoinhibitory element of Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two energetically coupled processes. The DH active site is directly, but weakly, inhibited by a helix from the adjacent Acidic domain. This core interaction is strengthened 10-fold by contacts of the calponin homology (CH) domain with the Acidic, pleckstrin homology, and DH domains. This construction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt the modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and consequent GEF activation. Our findings illustrate how the opposing requirements of strong suppression of activity and rapid kinetics of activation can be achieved in multidomain systems.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21422296

S.Y.Chen, P.H.Huang, and H.J.Cheng (2011).
Disrupted-in-Schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling.

Proc Natl Acad Sci U S A, 108, 5861-5866.

20842712

C.Kintscher, S.Wuertenberger, R.Eylenstein, T.Uhlendorf, and Y.Groemping (2010).
Autoinhibition of GEF activity in Intersectin 1 is mediated by the short SH3-DH domain linker.

Protein Sci, 19, 2164-2174.

20585582

K.F.Ahmad, and W.A.Lim (2010).
The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.

PLoS One, 5, e11291.

PDB code:

3jv3

20485291

W.A.Lim (2010).
Designing customized cell signalling circuits.

Nat Rev Mol Cell Biol, 11, 393-403.

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.