Mechanism of Microtubule Dynamics Regulation by Kinesins

驱动蛋白是真核细胞骨架蛋白，以其运动活性而闻名，但它们也是 微管动力学的重要调节剂，微管聚合物生长的能力或 心理医生该项目旨在建立分子机制和适应性， 驱动蛋白超家族的不同成员沿沿着微管移动或调节 微管动力学驱动蛋白对微管动力学的调节在细胞凋亡中起重要作用。 多种细胞过程，如有丝分裂、胞质分裂、神经发育和纤毛的控制 和中心粒长度，但这些驱动蛋白稳定或不稳定的机制 微管仍然不完全清楚。驱动蛋白诱导什么样的构象变化也不清楚 以及这些构象变化是否通过 微管蛋白的功能是变构地调节驱动蛋白和其他蛋白质沿沿着的结合。 为了解决这些问题，我们将进行冷冻电子显微镜结构和功能 运动和微管解聚酶驱动蛋白及其对微管作用的研究 结构本研究的目的分为三个方面：1）确定驱动蛋白的变构效应 结合微管结构和功能。2)确定联合运动的机制 和微管解聚活性。3)确定不同的起源 微管解聚酶驱动蛋白之间的功能。

Kinesins are eukaryotic cytoskeletal proteins best known for their motile activity, but they are also important regulators of microtubule dynamics, the ability of the microtubule polymer to grow or shrink. This project seeks to establish the molecular mechanisms and adaptations that allows different members of the kinesin superfamily to move along microtubules or to modulate microtubule dynamics. Regulation of microtubule dynamics by kinesins play important roles in a variety of cell processes such as mitosis, cytokinesis, neural development and the control of cilia and centriole length, but the mechanisms by which these kinesins stabilize or destabilize microtubules is still not fully clear. It is also not clear what conformational changes kinesins induce on the microtubule and whether these conformational changes are transmitted through the microtubule to allosterically modulate the binding of kinesin and other proteins along microtubules. To address these questions, we will perform cryo-electron microscopy structural and functional studies of motile and microtubule depolymerase kinesins, and their effect on microtubule structure. The proposal is divided into three aims: 1) Determine the allosteric effects of kinesin binding on microtubule structure and function. 2) Determine the mechanism of combined motile and microtubule depolymerization activities of Kinesin-8s. 3) Determine the origin of different functionalities among microtubule depolymerase kinesins.