Phichith Denis, Travaglia Mirko, Yang Zhaohui, Liu Xiaoyan, Zong Alan B, Safer Daniel, Sweeney H Lee
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17320-4. doi: 10.1073/pnas.0909748106. Epub 2009 Sep 28.
Although myosin VI has properties that would allow it to function optimally as a dimer, full-length myosin VI exists as a monomer in isolation. Based on the ability of myosin VI monomers to dimerize when held in close proximity, we postulated that cargo binding normally regulates dimerization of myosin VI. We tested this hypothesis by expressing a known dimeric cargo adaptor protein of myosin VI, optineurin, and the myosin VI-binding segment from a monomeric cargo adaptor protein, Dab2. In the presence of these adaptor proteins, full-length myosin VI has ATPase properties of a dimer, appears as a dimer in electron micrographs, and moves processively on actin filaments. The results support a model in which cargo binding exposes internal dimerization sequences within full-length myosin VI. Because, unexpectedly, a monomeric fragment of Dab2 triggers dimerization, it would appear that myosin VI is designed to function as a dimer in cells.
尽管肌球蛋白VI具有使其作为二聚体发挥最佳功能的特性，但全长肌球蛋白VI单独存在时为单体形式。基于肌球蛋白VI单体在紧密靠近时能够二聚化的能力，我们推测货物结合通常会调节肌球蛋白VI的二聚化。我们通过表达已知的肌球蛋白VI二聚体货物衔接蛋白视紫质神经元以及单体货物衔接蛋白Dab2的肌球蛋白VI结合片段来验证这一假设。在这些衔接蛋白存在的情况下，全长肌球蛋白VI具有二聚体的ATP酶特性，在电子显微镜下呈现为二聚体，并在肌动蛋白丝上进行持续性移动。这些结果支持了一种模型，即货物结合会暴露全长肌球蛋白VI内部的二聚化序列。由于出乎意料的是，Dab2的单体片段会触发二聚化，因此似乎肌球蛋白VI在细胞中被设计为以二聚体形式发挥作用。
