Mechanism of actin filament severing and capping by gelsolin

Abstract

Gelsolin is the prototypical member of a family of Ca2+-activated F-actin severing and capping proteins. Here we report structures of Ca2+-bound human gelsolin at the barbed end of F-actin. One structure reveals gelsolin’s six domains (G1G6) and interdomain linkers wrapping around F-actin, while another shows domains G1G3—a fragment observed during apoptosis—binding on both sides of F-actin. Conformational changes that trigger severing occur on one side of F-actin with G1G6 and on both sides with G1G3. Gelsolin remains bound after severing, blocking subunit exchange. The authors use cryo-electron microscopy to reveal two structural states of Ca2+-activated gelsolin bound to the actin filament, illuminating the mechanisms of filament severing and barbed end capping.