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: 10348652
• 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 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10348652
• 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.

项目总结

项目成果

The mechanism of kinesin inhibition by kinesin-binding protein.

驱动蛋白结合蛋白抑制运动蛋白的机制。

• DOI: 10.7554/elife.61481
• 发表时间: 2020-11-30
• 期刊: eLife
• 影响因子: 7.7
• 作者: Atherton J;Hummel JJ;Olieric N;Locke J;Peña A;Rosenfeld SS;Steinmetz MO;Hoogenraad CC;Moores CA
• 通讯作者: Moores CA