Structural Insights into Formation of an Active Signaling Complex between Rac and Phospholipase C Gamma 2

被引：57

作者：

Bunney, Tom D. ^{[1
]}

Opaleye, Olaniyi ^{[2
]}

Roe, S. Mark ^{[2
]}

Vatter, Petra ^{[3
]}

Baxendale, Rhona W. ^{[1
]}

Walliser, Claudia ^{[3
]}

Everett, Katy L. ^{[1
]}

Josephs, Michelle B. ^{[1
]}

Christow, Carolin ^{[3
]}

Rodrigues-Lima, Fernando ^{[4
]}

Gierschik, Peter ^{[3
]}

Pearl, Laurence H. ^{[2
]}

Katan, Matilda ^{[1
]}

机构：

[1] Inst Canc Res, Sect Cell & Mol Biol, London SW3 6JB, England

[2] Inst Canc Res, Sect Struct Biol, Chester Beatty Labs, London SW3 6JB, England

[3] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, D-89070 Ulm, Germany

[4] Univ Paris 07, CNRS, Lab Mol & Cellular Responses Xenobiot, Unit Funct & Adapt Biol BFA, F-75013 Paris, France

来源：

MOLECULAR CELL | 2009年 / 34卷 / 02期

关键词：

GTPASE-BINDING DOMAIN; RHO-GTPASES; CRYSTAL-STRUCTURE; EFFECTOR PROTEINS; FAMILY; STIMULATION; SWITCH; CDC42; TRANSDUCTION; C-GAMMA(2);

D O I：

10.1016/j.molcel.2009.02.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Rho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of the complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2) (PLC gamma(2)). Based on this structure, we illustrate distinct requirements for PLC gamma(2) activation by Rac and EGF and generate Rac effector mutants that specifically block activation of PLC gamma(2), but not the related PLC beta(2) isoform. Furthermore, in addition to the complex, we report the crystal structures of free spPH and Rac2 bound to GDP and GTP gamma S. These structures illustrate a mechanism of conformational switches that accompany formation of signaling active complexes and highlight the role of effector binding as a common feature of Rac and Cdc42 interactions with a variety of effectors.

引用

页码：223 / 233

页数：11

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