Structural insights into the regulation of actin capping protein by twinfilin C-terminal tail
Structural insights into the regulation of actin capping protein by twinfilin C-terminal tail
复制标题
Twinfilin C 末端尾部对肌动蛋白加帽蛋白的调节的结构见解
DOI：
10.1016/j.jmb.2021.166891
复制
发表时间：
2021
期刊：
影响因子：
5.6
通讯作者：
Motonori Ota and Yuichiro Maeda
中科院分区：
文献类型：
--
作者：
Shuichi Takeda;Ryotaro Koike;Ikuko Fujiwara;Akihiro Narita;Makoto Miyata;Motonori Ota and Yuichiro Maeda
Twinfilin是一种保守的肌动蛋白调节因子，其通过C末端残基（TWtail）与肌动蛋白加帽蛋白（CP）相互作用，所述C末端残基与CARMIL的CP相互作用（CPI）基序具有序列相似性。在这里，我们报告的晶体结构的TWtail在复杂的CP。我们的结构表明，虽然TWtail和CARMIL CPI通过其中间区域将CP结合到重叠表面，但它们在两端表现出不同的CP结合模式。因此，TWtail和CARMIL CPI分别以开放和封闭形式的不同构象限制CP。有趣的是，V-1靶向远离TWtail结合位点的CP，也有利于开放形式的CP。一致地，TWtail与CP和V-1形成稳定的三元复合物，这与CARMIL CPI形成鲜明对比，后者迅速将V-1与CP解离。我们的研究结果表明，TWtail是一个独特的CP结合基序，调节CP的方式不同于CARMIL CPI。
Twinfilin is a conserved actin regulator that interacts with actin capping protein (CP) via C terminus residues (TWtail) that exhibits sequence similarity with the CP interaction (CPI) motif of CARMIL. Here we report the crystal structure of TWtail in complex with CP. Our structure showed that although TWtail and CARMIL CPI bind CP to an overlapping surface via their middle regions, they exhibit different CP-binding modes at both termini. Consequently, TWtail and CARMIL CPI restrict the CP in distinct conformations of open and closed forms, respectively. Interestingly, V-1, which targets CP away from the TWtail binding site, also favors the open-form CP. Consistently, TWtail forms a stable ternary complex with CP and V-1, a striking contrast to CARMIL CPI, which rapidly dissociates V-1 from CP. Our results demonstrate that TWtail is a unique CP-binding motif that regulates CP in a manner distinct from CARMIL CPI.