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Structure paper

タイトル	Molecular mechanism of actin filament elongation by formins.
ジャーナル・号・ページ	Science, Vol. 384, Issue 6692, Page eadn9560, Year 2024
掲載日	2024年4月12日
著者	Wout Oosterheert / Micaela Boiero Sanders / Johanna Funk / Daniel Prumbaum / Stefan Raunser / Peter Bieling /
PubMed 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.
リンク	Science / PubMed:38603491
手法	EM (単粒子)
解像度	3.08 - 6.25 Å
構造データ	EMDB-19497: Cryo-EM reconstruction of the formin Cdc12 bound to the barbed end of F-actin (without phalloidin) 手法: EM (単粒子) / 解像度: 4.54 Å 19499 8rty EMDB-19499, PDB-8rty: Structure of the F-actin barbed end bound by Cdc12 and profilin (ring complex) at a resolution of 6.3 Angstrom 手法: EM (単粒子) / 解像度: 6.25 Å 19501 8ru0 EMDB-19501, PDB-8ru0: Structure of the undecorated barbed end of F-actin. 手法: EM (単粒子) / 解像度: 3.08 Å 19503 8ru2 EMDB-19503, PDB-8ru2: Structure of the F-actin barbed end bound by formin mDia1 手法: EM (単粒子) / 解像度: 3.49 Å 19522 8rv2 EMDB-19522, PDB-8rv2: Structure of the formin INF2 bound to the barbed end of F-actin. 手法: EM (単粒子) / 解像度: 3.41 Å
化合物	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM / アデノシン二リン酸 ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-PO4: PHOSPHATE ION / ホスファ-ト / リン酸塩 ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸
由来	homo sapiens (ヒト) schizosaccharomyces pombe (分裂酵母) amanita phalloides (タマゴテングタケ) oryctolagus cuniculus (ウサギ) mus musculus (ハツカネズミ)
キーワード	STRUCTURAL PROTEIN (タンパク質) / actin (アクチン) / formin / Cdc12 / profilin (プロフィリン) / actin assembly (アクチン) / actin end / barbed end / INF2