1F5X

NMR STRUCTURE OF THE Y174 AUTOINHIBITED DBL HOMOLOGY DOMAIN

1F5X の概要

• エントリーDOI: 10.2210/pdb1f5x/pdb
• 分子名称: RHO-GEF VAV (1 entity in total)
• 機能のキーワード: 11 alpha-helices, signaling protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24490.31

構造登録者

Aghazadeh, B.,Rosen, M.K.,Lowry, W.E.,Huang, X.Y. (登録日: 2000-06-18, 公開日: 2000-09-15, 最終更新日: 2024-05-22)

主引用文献

Aghazadeh, B.,Lowry, W.E.,Huang, X.Y.,Rosen, M.K.
Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation.
Cell(Cambridge,Mass.), 102:625-633, 2000

PubMed 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.

PubMed: 11007481
DOI: 10.1016/S0092-8674(00)00085-4

実験手法

SOLUTION NMR