ジャーナル: Science / 年: 2024 タイトル: Molecular mechanism of actin filament elongation by formins. 著者: Wout Oosterheert / Micaela Boiero Sanders / Johanna Funk / Daniel Prumbaum / Stefan Raunser / Peter Bieling / 要旨: Formins control the assembly of actin filaments (F-actin) that drive cell morphogenesis and motility in eukaryotes. However, their molecular interaction with F-actin and their mechanism of action ...Formins control the assembly of actin filaments (F-actin) that drive cell morphogenesis and motility in eukaryotes. However, their molecular interaction with F-actin and their mechanism of action remain unclear. In this work, we present high-resolution cryo-electron microscopy structures of F-actin barbed ends bound by three distinct formins, revealing a common asymmetric formin conformation imposed by the filament. Formation of new intersubunit contacts during actin polymerization sterically displaces formin and triggers its translocation. This "undock-and-lock" mechanism explains how actin-filament growth is coordinated with formin movement. Filament elongation speeds are controlled by the positioning and stability of actin-formin interfaces, which distinguish fast and slow formins. Furthermore, we provide a structure of the actin-formin-profilin ring complex, which resolves how profilin is rapidly released from the barbed end during filament elongation.
Power-adjusted map of actin-Cdc12 with phalloidin(EMD-19496), resampled on the no-phalloidin map. Used to construct a difference map between the reconstructions with and without phalloidin.
全体 : Complex of the dimeric FH2 domain of S. Pombe Cdc12 bound to the ...
全体
名称: Complex of the dimeric FH2 domain of S. Pombe Cdc12 bound to the barbed end of F-actin.
要素
複合体: Complex of the dimeric FH2 domain of S. Pombe Cdc12 bound to the barbed end of F-actin.
複合体: Actin filament
タンパク質・ペプチド: human cytoplasmic beta-actin
複合体: Dimeric FH2 domain of S. Pombe Cdc12
タンパク質・ペプチド: S. pombe Cdc12
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超分子 #1: Complex of the dimeric FH2 domain of S. Pombe Cdc12 bound to the ...
超分子
名称: Complex of the dimeric FH2 domain of S. Pombe Cdc12 bound to the barbed end of F-actin. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Human beta-actin and S. Pombe Cdc12 were purified separately. Both proteins were mixed to assemble the complex prior to cryo-EM grid preparation.