Branching out: Arp2/3 (red and green) can nucleate branches from filaments of actin (pink).


Biochemical and kinetic studies have failed to provide a unified view on how the Arp2/3 complex nucleates actin filaments. Does the complex, which mediates actin filament nucleation and branch formation at the leading edge of motile cells, bind to the side of an older actin filament, or does it become incorporated into that filament?

Structural studies now add anew dimension to the discourse, supporting the side-binding, dendritic nucleation model. These studies provide visual evidence that the seven subunit actin-related protein (Arp) complex is not inserted into the mother filament during actin filament nucleation in Acanthamoeba castellanii and Saccharomyces cerevisiae. Additionally, and rather unexpectedly, imaging by electron cryomicroscopy provides evidence that the Arp2/3 complex undergoes a major conformational change during branch formation.

This rearrangement of the complex was “rather surprising to see,” says Dorit Hanein (The Burnham Institute, La Jolla, CA). Hanein describes her work with Niels Volkmann and colleagues as the “first serious attempt to look at the structural changes associated with the mechanism of actin nucleation by Arp2/3 complex.” The group's approach incorporates various electron microscopy imaging techniques combined with single particle analysis of activated Arp2/3 complexes and image analysis of Arp2/3 in actin filament branch junctions. The structural findings provide direct evidence that Arp2 and Arp3 form the first two subunits of the developing daughter filament. ▪


Volkmann, N., et al. 2001. Science. 10.1126/science.1063025