Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles
复制标题
DOI：
10.1016/j.celrep.2014.07.041
复制
发表时间：
2014-09-11
期刊：
影响因子：
8.8
通讯作者：
Sweeney, H. Lee
中科院分区：
文献类型：
--
作者：
Mukherjea, Monalisa;Ali, M. Yusuf;Sweeney, H. Lee
目前还不清楚反向肌球蛋白（肌球蛋白VI）是否作为单体或二聚体在细胞中发挥作用，以及它如何在肌动蛋白上产生大的运动。我们删除了一个稳定的单α-螺旋（SAH）结构域，该结构域被认为是杠杆臂的一部分，可以放大运动，而不会影响体外运动或体内功能。使用该SAH结构域作为其杠杆臂的一部分的肌球蛋白VI构建体能够在体外采取大的步骤，但不能挽救体内功能。这是必要的肌球蛋白VI内部二聚化，触发展开的三螺旋束和钙调蛋白结合，以正常的步骤在体外和救援内吞和高尔基体形态肌球蛋白VI空成纤维细胞。肌球蛋白VI的模型出现，其中货物结合触发二聚化并展开三螺旋束以创建体内功能所必需的杠杆臂。
It is unclear whether the reverse-direction myosin (myosin VI) functions as a monomer or dimer in cells and how it generates large movements on actin. We deleted a stable, single-a-helix (SAH) domain that has been proposed to function as part of a lever arm to amplify movements without impact on in vitro movement or in vivo functions. A myosin VI construct that used this SAH domain as part of its lever arm was able to take large steps in vitro but did not rescue in vivo functions. It was necessary for myosin VI to internally dimerize, triggering unfolding of a three-helix bundle and calmodulin binding in order to step normally in vitro and rescue endocytosis and Golgi morphology in myosin VI-null fibroblasts. A model for myosin VI emerges in which cargo binding triggers dimerization and unfolds the three-helix bundle to create a lever arm essential for in vivo functions.