Tuning Mitotic Kinesins Through Motor Domain Post Translational Modifications

通过运动域翻译后修饰调节有丝分裂驱动蛋白

• 批准号: 9893924
• 负责人: STEVEN P GROSS
• 金额: $ 57.87万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893924
• 关键词: ATP phosphohydrolase; Acetylation; Affect; Antibodies; Behavior; Binding; Biological; Biological Assay; Biophysics; Cell Cycle; Cell model; Cells; Cellular biology; Communication; Complex; Coupled; Couples; Coupling; Development; Disease; Environment; Fibrosis; Fluorescence Resonance Energy Transfer; In Vitro; Kinesin; Kinetics; Lead; Length; Libraries; Location; Measures; Mechanics; Microtubules; Mitosis; Mitotic; Mitotic spindle; Molecular Conformation; Monte Carlo Method; Motor; Motor output; Movement; Mutation; Neck; Nucleotides; Pathologic; Pathway interactions; Phage Display; Physiological; Physiology; Play; Post-Translational Protein Processing; Preparation; Proliferating; Role; SWI1; Structure; Testing; Time; Work; cancer therapy; chromosome movement; live cell imaging; mechanical behavior; mimetics; mutant; novel; novel therapeutics; predictive test; single molecule

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.

项目概要 许多有丝分裂驱动蛋白在有丝分裂中发挥多种作用——每种作用可能需要不同的机械行为。 这种多功能性意味着细胞需要能够“微调”这些马达。 有丝分裂驱动蛋白运动域 (MD) 的翻译修饰 (PTM) 发挥着这一作用。 PTM 存在于许多有丝分裂驱动蛋白中，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。 结合瞬态动力学、单分子力学和细胞生物学来研究 MD PTM 的作用 影响三种多功能驱动蛋白——Kif11、Kif18A 和 Kif22。 开发一个集成模型来了解细胞如何调节其驱动蛋白以满足不同的需求。