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EMBO J. 2012 Jan 4;31(1):236-47. doi: 10.1038/emboj.2011.343. Epub 2011 Sep 20.

Three-dimensional reconstructions of Arp2/3 complex with bound nucleation promoting factors.

Author information

1
Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.

Abstract

Arp2/3 complex initiates the growth of branched actin-filament networks by inducing actin polymerization from the sides of pre-existing filaments. Nucleation promoting factors (NPFs) are essential for the branching reaction through interactions with the Arp2/3 complex prior to branch formation. The modes by which NPFs bind Arp2/3 complex and associated conformational changes have remained elusive. Here, we used electron microscopy to determine three-dimensional structures at ~2 nm resolution of Arp2/3 complex with three different bound NPFs: N-WASp, Scar-VCA and cortactin. All of these structures adopt a conformation with the two actin-related proteins in an actin-filament-like dimer and the NPF bound to the pointed end. Distance constraints derived by fluorescence resonance energy transfer independently verified the NPF location. Furthermore, all bound NPFs partially occlude the actin-filament binding site, suggesting that additional local structural rearrangements are required in the pathway of Arp2/3 complex activation to allow branch formation.

PMID:
21934650
PMCID:
PMC3252567
DOI:
10.1038/emboj.2011.343
[Indexed for MEDLINE]
Free PMC Article

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