Tuning Mitotic Kinesins Through Motor Domain Post Translational Modifications

项目总结 许多有丝分裂动蛋白在有丝分裂中扮演着多种角色--每一种都可能需要不同的机械行为。 这种多功能意味着细胞需要能够“微调”这些马达。我们建议邮寄- 有丝分裂动蛋白运动区(MD)的翻译修饰(PTM)起到这一作用。这些 PTM存在于许多有丝分裂动蛋白中，它们聚集在形成变构途径的结构中 它将核苷酸和微管结合到运动中。在这项提案中，我们将应用 结合瞬变动力学、单分子力学和细胞生物学来研究MD PTMS是如何 影响三种多功能Kinesin-Kif11、Kif18A和Kif22。这些研究的结果应该能让我们 为细胞如何调节它们的动蛋白以满足不同的需求开发一个综合模型。

PROJECT SUMMARY Many mitotic kinesins play multiple roles in mitosis—each likely requiring distinct mechanical behavior. This multi-functionality implies that cells need to be able to “fine tune” these motors. We propose that post- translational modifications (PTMs) of the motor domain (MD) of mitotic kinesins serve this role. These PTMs are found in many mitotic kinesins and they cluster in structures that form an allosteric pathway which couples nucleotide and microtubule binding to movement. In this proposal, we will apply a combination of transient kinetics, single molecule mechanics, and cell biology to examine how MD PTMs affect three multifunctional kinesins—Kif11, Kif18A, and Kif22. Results of these studies should allow us to develop an integrated model for how cells modulate their kinesins to meet diverse needs.