アクチンのフィラメント構造と重合機構 ―重合によるATPase活性化のメカニズム―

抄録

Actin assembly activates ATP hydrolysis, which provides structural cues for flament turnover. Polymerized actin supports cellular signaling, intracellular trafficking, and cytokinesis. We present the cryo-electron microscopic structure of F-actin in the presence of phosphate, with the visualization of some α-helical backbones and large side chains. A complete atomic model based on the cryo-EM identified intermolecular interactions, some of which were mediated by magnesium or phosphate ions. A critical role for bending of the proline-rich loop (residues 108-112) in activating ATPase was revealed. Crystal structures of G-actin mutants, which trap the catalytic site in two intermediate states, were solved. These structures combined with cryo-EM data allows us to propose a molecular mechanism for actin assembly and ATPase activation, critical for filament dynamics.