Arp2/3 complex is bound and activated by two WASP proteins

被引：158
|
作者：
Padrick, Shae B. [1 ,2 ]
Doolittle, Lynda K. [1 ,2 ]
Brautigam, Chad A. [1 ,2 ]
King, David S. [3 ,4 ]
Rosen, Michael K. [1 ,2 ]
机构：
[1] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA
[3] Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 33期
基金：
美国国家卫生研究院;
关键词：
ALDRICH-SYNDROME PROTEIN; WASP/SCAR PROTEINS; ACTIN NUCLEATION; STRUCTURAL BASIS; CONFORMATIONAL-CHANGES; FAMILY PROTEINS; N-WASP; FILAMENT; SUBUNIT; BINDING;
D O I：
10.1073/pnas.1100236108
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Actin related protein 2/actin related protein 3 (Arp2/3) complex nucleates new actin filaments in eukaryotic cells in response to signals from proteins in the Wiskott-Aldrich syndrome protein (WASP) family. The conserved VCA domain of WASP proteins activates Arp2/3 complex by inducing conformational changes and delivering the first actin monomer of the daughter filament. Previous models of activation have invoked a single VCA acting at a single site on Arp2/3 complex. Here we show that activation most likely involves engagement of two distinct sites on Arp2/3 complex by two VCA molecules, each delivering an actin monomer. One site is on Arp3 and the second is on ARPC1 and Arp2. The VCAs at these sites have distinct roles in activation. Our findings reconcile apparently conflicting literature on VCA activation of Arp2/3 complex and lead to a new model for this process.
引用
收藏
页码：E472 / E479
页数：8
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