Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17388-93. doi: 10.1073/pnas.1208642109. Epub 2012 Sep 10.
Processive movements of unconventional myosins on actin filaments generally require motor dimerization. A commonly accepted myosin dimerization mechanism is via formation of a parallel coiled-coil dimer by a stretch of amino acid residues immediately carboxyl-terminal to the motor's lever-arm domain. Here, we discover that the predicted coiled-coil region of myosin X forms a highly stable, antiparallel coiled-coil dimer (anti-CC). Disruption of the anti-CC either by single-point mutations or by replacement of the anti-CC with a parallel coiled coil with a similar length compromised the filopodial induction activity of myosin X. We further show that the anti-CC and the single α-helical domain of myosin X are connected by a semirigid helical linker. The anti-CC-mediated dimerization may enable myosin X to walk on both single and bundled actin filaments.
非常规肌球蛋白在肌动蛋白丝上的进行性运动通常需要肌球蛋白二聚化。一种被广泛接受的肌球蛋白二聚化机制是通过位于马达杆状结构域羧基末端的一段氨基酸残基形成平行的卷曲螺旋二聚体。在这里，我们发现肌球蛋白 X 的预测卷曲螺旋区形成了一个高度稳定的、反平行卷曲螺旋二聚体（anti-CC）。通过单点突变或用类似长度的平行卷曲螺旋替换 anti-CC 破坏了 anti-CC，从而损害了肌球蛋白 X 的丝状伪足诱导活性。我们进一步表明，肌球蛋白 X 的 anti-CC 和单个α螺旋结构域之间由一个半刚性螺旋连接子连接。anti-CC 介导的二聚化可能使肌球蛋白 X 能够在单根和束状肌动蛋白丝上行走。
