ジャーナル: Nat Commun / 年: 2024 タイトル: Phalloidin and DNase I-bound F-actin pointed end structures reveal principles of filament stabilization and disassembly. 著者: Micaela Boiero Sanders / Wout Oosterheert / Oliver Hofnagel / Peter Bieling / Stefan Raunser / 要旨: Actin filament turnover involves subunits binding to and dissociating from the filament ends, with the pointed end being the primary site of filament disassembly. Several molecules modulate filament ...Actin filament turnover involves subunits binding to and dissociating from the filament ends, with the pointed end being the primary site of filament disassembly. Several molecules modulate filament turnover, but the underlying mechanisms remain incompletely understood. Here, we present three cryo-EM structures of the F-actin pointed end in the presence and absence of phalloidin or DNase I. The two terminal subunits at the undecorated pointed end adopt a twisted conformation. Phalloidin can still bind and bridge these subunits, inducing a conformational shift to a flattened, F-actin-like state. This explains how phalloidin prevents depolymerization at the pointed end. Interestingly, two DNase I molecules simultaneously bind to the phalloidin-stabilized pointed end. In the absence of phalloidin, DNase I binding would disrupt the terminal actin subunit packing, resulting in filament disassembly. Our findings uncover molecular principles of pointed end regulation and provide structural insights into the kinetic asymmetry between the actin filament ends.
超分子 #1: Actin filament pointed end bound by phalloidin
超分子
名称: Actin filament pointed end bound by phalloidin / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 詳細: Human beta-actin was purified recombinantly, phalloidin (from Amanita phalloides) was bought from sigma. The components were mixed to assemble the complex prior to cryo-EM grid preparation.
-
超分子 #2: Actin filament pointed end
超分子
名称: Actin filament pointed end / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1 詳細: The four terminal subunits of the pointed end of the actin filament.
由来(天然)
生物種: Homo sapiens (ヒト)
-
超分子 #3: Phalloidin
超分子
名称: Phalloidin / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2 詳細: Toxin from Amanita phalloides that stabilizes the actin filament