8A2U

Cryo-EM structure of F-actin in the Ca2+-ADP-BeF3- nucleotide state.

8A2U の概要

• エントリーDOI: 10.2210/pdb8a2u/pdb
• 関連するPDBエントリー: 8A2R 8A2S
• EMDBエントリー: 15104 15105 15107
• 分子名称: Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: actin, cytoskeleton, filament, nucleotide state, structural protein
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 212044.60

構造登録者

Oosterheert, W.,Klink, B.U.,Belyy, A.,Pospich, S.,Raunser, S. (登録日: 2022-06-06, 公開日: 2022-08-10, 最終更新日: 2022-11-23)

主引用文献

Oosterheert, W.,Klink, B.U.,Belyy, A.,Pospich, S.,Raunser, S.
Structural basis of actin filament assembly and aging.
Nature, 611:374-379, 2022

PubMed Abstract: The dynamic turnover of actin filaments (F-actin) controls cellular motility in eukaryotes and is coupled to changes in the F-actin nucleotide state. It remains unclear how F-actin hydrolyses ATP and subsequently undergoes subtle conformational rearrangements that ultimately lead to filament depolymerization by actin-binding proteins. Here we present cryo-electron microscopy structures of F-actin in all nucleotide states, polymerized in the presence of Mg or Ca at approximately 2.2 Å resolution. The structures show that actin polymerization induces the relocation of water molecules in the nucleotide-binding pocket, activating one of them for the nucleophilic attack of ATP. Unexpectedly, the back door for the subsequent release of inorganic phosphate (P) is closed in all structures, indicating that P release occurs transiently. The small changes in the nucleotide-binding pocket after ATP hydrolysis and P release are sensed by a key amino acid, amplified and transmitted to the filament periphery. Furthermore, differences in the positions of water molecules in the nucleotide-binding pocket explain why Ca-actin shows slower polymerization rates than Mg-actin. Our work elucidates the solvent-driven rearrangements that govern actin filament assembly and aging and lays the foundation for the rational design of drugs and small molecules for imaging and therapeutic applications.

PubMed: 36289337
DOI: 10.1038/s41586-022-05241-8

実験手法

ELECTRON MICROSCOPY (2.21 Å)