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

被引：159
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
相关论文
共 43 条
[1]  
[Anonymous], 2003, Molecular Driving Forces: Statistical Thermodynamics in Chemistry Biology
[2]   Studying multiprotein complexes by multisignal sedimentation velocity analytical ultracentrifugation [J].
Balbo, A ;
Minor, KH ;
Velikovsky, CA ;
Mariuzza, RA ;
Peterson, CB ;
Schuck, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (01) :81-86
[3]   The p40/ARPC1 Subunit of Arp2/3 Complex Performs Multiple Essential Roles in WASp-regulated Actin Nucleation [J].
Balcer, Heath I. ;
Daugherty-Clarke, Karen ;
Goode, Bruce L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (11) :8481-8491
[4]   Identification of functionally important residues of Arp2/3 complex by analysis of homology models from diverse species [J].
Beltzner, CC ;
Pollard, TD .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 336 (02) :551-565
[5]   Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins [J].
Blanchoin, L ;
Amann, KJ ;
Higgs, HN ;
Marchand, JB ;
Kaiser, DA ;
Pollard, TD .
NATURE, 2000, 404 (6781) :1007-1011
[6]   X-ray scattering study of activated Arp2/3 complex with bound actin-WCA [J].
Boczkowska, Malgorzata ;
Rebowski, Grzegorz ;
Petoukhov, Maxim V. ;
Hayes, David B. ;
Svergun, Dmitri I. ;
Dominguez, Roberto .
STRUCTURE, 2008, 16 (05) :695-704
[7]   Subunit and Catalytic Component Stoichiometries of an in Vitro Reconstituted Human Pyruvate Dehydrogenase Complex [J].
Brautigam, Chad A. ;
Wynn, R. Max ;
Chuang, Jacinta L. ;
Chuang, David T. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (19) :13086-13098
[8]   Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly [J].
Chereau, D ;
Kerff, F ;
Graceffa, P ;
Grabarek, Z ;
Langsetmo, K ;
Dominguez, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (46) :16644-16649
[9]   Activation of Arp2/3 complex: Addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2 [J].
Dayel, MJ ;
Mullins, RD .
PLOS BIOLOGY, 2004, 2 (04) :476-485
[10]   Critical conformational changes in the Arp2/3 complex are induced by nucleotide and nucleation promoting factor [J].
Goley, ED ;
Rodenbusch, SE ;
Martin, AC ;
Welch, MD .
MOLECULAR CELL, 2004, 16 (02) :269-279
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