Structure of the nucleation‐promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex

摘要

Unlike the family of Arp2/3 complex activators, / / 90 ( ) family proteins activate actin filament nucleation by the Arp2/3 complex without the need for a preformed actin filament. This allows proteins to initiate branched actin network assembly by providing seed filaments that activate ‐bound Arp2/3 complex. Despite their important role in actin network initiation, it is unclear how proteins drive the activating steps that require both WASP and pre‐existing actin filaments during ‐mediated nucleation. Here, we show that 90 folds into an armadillo repeat domain that binds a surface of Arp2/3 complex distinct from the two sites, straddling a hinge point that may stimulate movement of the Arp2 subunit into the activated short‐pitch conformation. 90 binds a surface on Arp2/3 complex that overlaps with actin filament binding, explaining how it could stimulate the same structural rearrangements in the complex as pre‐existing actin filaments. By revealing how proteins activate the Arp2/3 complex, these data provide a molecular foundation to understand initiation of dendritic actin networks and regulation of Arp2/3 complex by its activators.