Park Hyokeun, Ramamurthy Bhagavathi, Travaglia Mirko, Safer Dan, Chen Li-Qiong, Franzini-Armstrong Clara, Selvin Paul R, Sweeney H Lee
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Mol Cell. 2006 Feb 3;21(3):331-6. doi: 10.1016/j.molcel.2005.12.015.
Myosin VI is a reverse direction actin-based motor capable of taking large steps (30-36 nm) when dimerized. However, all dimeric myosin VI molecules so far examined have included non-native coiled-coil sequences, and reports on full-length myosin VI have failed to demonstrate the existence of dimers. Herein, we demonstrate that full-length myosin VI is capable of forming stable, processive dimers when monomers are clustered, which move up to 1-2 mum in approximately 30 nm, hand-over-hand steps. Furthermore, we present data consistent with the monomers being prevented from dimerizing unless they are held in close proximity and that dimerization is somewhat inhibited by the cargo binding tail. A model thus emerges that cargo binding likely clusters and initiates dimerization of full-length myosin VI molecules. Although this mechanism has not been previously described for members of the myosin superfamily, it is somewhat analogous to the proposed mechanism of dimerization for the kinesin Unc104.
肌球蛋白VI是一种基于肌动蛋白的反向运动蛋白，二聚化时能够迈出大步（30 - 36纳米）。然而，迄今为止所检测的所有二聚体肌球蛋白VI分子都包含非天然的卷曲螺旋序列，并且关于全长肌球蛋白VI的报道未能证明二聚体的存在。在此，我们证明当单体聚集时，全长肌球蛋白VI能够形成稳定的、进行性的二聚体，这些二聚体以大约30纳米的手拉手步幅移动高达1 - 2微米。此外，我们提供的数据表明，除非单体紧密靠近，否则它们会被阻止二聚化，并且货物结合尾部会在一定程度上抑制二聚化。由此出现了一个模型，即货物结合可能会使全长肌球蛋白VI分子聚集并启动二聚化。尽管这种机制以前尚未在肌球蛋白超家族成员中描述过，但它在某种程度上类似于所提出的驱动蛋白Unc104的二聚化机制。
