Structure of Arp2/3 complex in its activated state and in actin filament branch junctions

The seven-subunit Arp2/3 complex choreographs the formation of branched act in networks at the leading edge of migrating cells. When activated by Wisko tt-Aldrich Syndrome protein (WASp), the Arp2/3 complex initiates actin fila ment branches from the sides of existing filaments. Electron cryomicroscopy and three-dimensional reconstruction of Acanthamoeba castellanil and Sacch aromyces cerevisiae Arp2/3 complexes bound to the WASp carboxy-terminal dom ain reveal asymmetric, oblate ellipsoids. Image analysis of actin branches indicates that the complex binds the side of the mother filament, and Arp2 and Arp3 (for actin-related protein) are the first two subunits of the daug hter filament. Comparison to the actin-free, WASp-activated complexes sugge sts that branch initiation involves large-scale structural rearrangements w ithin Arp2/3.