The structure of the actin filament uncapping complex mediated by twinfilin.
The structure of the actin filament uncapping complex mediated by twinfilin.
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DOI：
10.1126/sciadv.abd5271
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Robinson RC
中科院分区：
文献类型：
--
作者：
Mwangangi DM;Manser E;Robinson RC
加帽蛋白，twinfilin和肌动蛋白之间的竞争性相互作用驱动肌动蛋白丝脱帽和回收。去帽肌动蛋白丝是必不可少的驱动聚合和解聚动力学从帽蛋白相关的丝，然而，去帽导致快速拆卸的机制是未知的。在这里，我们阐明了肌动蛋白/twinfilin/加帽蛋白复合物的X射线晶体结构，以解决肌动蛋白丝的twinfilin脱帽机制。Twinfilin/加帽蛋白复合物与两个G-肌动蛋白亚基以类似于肌动蛋白丝倒刺末端的方向结合。这表明了一个意想不到的机制，twinfilin通过诱导两个末端肌动蛋白亚基中的G-肌动蛋白构象来破坏肌动蛋白丝的稳定帽。此外，twinfilin障碍关键肌动蛋白帽蛋白的相互作用，这将有助于在帽蛋白的解离，并可能通过第二种机制，涉及V-1竞争的肌动蛋白结合表面上的帽蛋白，促进丝脱帽。与帽蛋白的广泛相互作用表明，twinfilin的进化保守的作用是去帽肌动蛋白丝。
Competitive interactions between capping protein, twinfilin, and actin drive actin filament uncapping and recycling. Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein–associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments.
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影响因子：
7.7
作者：
Johnston AB;Hilton DM;McConnell P;Johnson B;Harris MT;Simone A;Amarasinghe GK;Cooper JA;Goode BL
通讯作者：
Goode BL
影响因子：
5.6
作者：
Hilton DM;Aguilar RM;Johnston AB;Goode BL
通讯作者：
Goode BL
影响因子：
4
作者：
Moseley, JB;Okada, K;Goode, BL
通讯作者：
Goode, BL
DOI：
10.1073/pnas.200199049167117
发表时间：
2020-08-18
影响因子：
11.1
作者：
Akil, Caner;Tran, Linh T.;Robinson, Robert C.
通讯作者：
Robinson, Robert C.
影响因子：
11.4
作者：
Helfer, E;Nevalainen, EM;Carlier, MF
通讯作者：
Carlier, MF