Molecular Mechanisms of Myosin-3

项目概要/摘要 我们的目标是确定肌球蛋白3马达的分子机制，肌球蛋白3马达是肌球蛋白中独特的激酶-肌球蛋白杂交体。 肌球蛋白超家族，参与基本的细胞过程，包括货物运输和 感觉细胞中肌动蛋白细胞骨架的组织。尽管它们在人类生物学中起着关键作用， 肌球蛋白-3马达的机制还不清楚。我们建议，不同的监管模式， 与不同的激酶底物和结合伴侣的相互作用决定了肌球蛋白-3马达的分子机制。 一个综合的和创新的生物化学，生物物理，细胞生物学和高分辨率的结构方法将 用于（i）确定酶谱和调节，（ii）独特的结构（iii）和途径， 在体外和细胞中控制肌球蛋白-3的功能和调节。总的来说，这些研究将揭示新的 对肌球蛋白-3马达的调节机制的见解，并在理解 不同的肌球蛋白是如何被调整来组织细胞中的肌动蛋白网络的。

PROJECT SUMMARY/ABSTRACT Our goal is to determine the molecular mechanisms of myosin-3 motors, unique kinase-myosin hybrids in the myosin superfamily, that are involved in fundamental cellular processes including cargo transport and the organization of the actin cytoskeleton in sensory cells. Despite their critical role in human biology, the molecular mechanisms of myosin-3 motors are not well understood. We propose that different modes of regulation together with different kinase substrates and binding partners determine the molecular mechanisms of myosin-3 motors. An integrated and innovative biochemical, biophysical, cell biological and high-resolution structural approach will be used to (i) determine the enzymatic profile and regulation, (ii) the unique structure (iii) and pathways that control myosin-3 function and regulation in vitro and in cells. Collectively, these studies will reveal novel mechanistic insights into the regulation of myosin-3 motors and have broad implications in the understanding of how different myosins are tuned to organize actin networks in cells.