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Single-molecule studies of kinesin biophysics using DNA-kinesin chimeras

使用 DNA-驱动蛋白嵌合体进行驱动蛋白生物物理学的单分子研究

基本信息

批准号：
BB/G019118/1
负责人：
Andrew Turberfield
金额：
$ 46.2万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG019118%2F1
关键词：
Single molecule studies kinesin biophysics

项目摘要

Kinesins are a family of motor proteins that have a wide range of functions including transport of molecular cargoes within cells, assembly and disassembly of networks of rigid microtubules that are used to organize cell contents, and the separation of chromosomes when cells divide. Conventional kinesin has two identical heads that can each bind to a microtubule. It 'walks' hand-over-hand, which requires coordination - it is important that at least one head remains bound at all times, otherwise the motor is likely to lose contact with its track. The mechanisms by which the motor coordinates its heads and generates force are still not clear. It is important to understand them, because defective kinesins can cause disease and because kinesin and microtubules are drug targets in some cancer therapies. We are studying the mechanism of kinesin by creating artificial motors incorporating elements of kinesin attached to frameworks assembled from short strands of DNA. This allows us to alter the number of kinesin heads that are working together, or the length or the elasticity of the link between them, in ways that are not possible when working with the natural protein alone. Our aims are to improve the precision of measurements of single kinesin molecules walking, to study how kinesin's heads are coordinated, and to investigate how many kinesins work together to create larger forces.

驱动蛋白是一类具有广泛功能的马达蛋白，包括在细胞内运输分子货物，组装和拆卸用于组织细胞内容物的刚性微管网络，以及在细胞分裂时分离染色体。传统的驱动蛋白有两个相同的头部，每个头部都可以与微管结合。它双手交替地“行走”，这需要协调-重要的是至少有一个头始终保持束缚，否则电机可能会失去与轨道的接触。电动机协调其头部并产生力的机制仍然不清楚。了解它们很重要，因为有缺陷的驱动蛋白会导致疾病，而且驱动蛋白和微管是某些癌症治疗的药物靶点。我们正在研究驱动蛋白的机制，通过创造人工马达，将驱动蛋白的元素连接到由短链DNA组装的框架上。这使我们能够改变一起工作的驱动蛋白头部的数量，或者它们之间连接的长度或弹性，而这在单独使用天然蛋白质时是不可能的。我们的目标是提高单个驱动蛋白分子行走的测量精度，研究驱动蛋白的头部是如何协调的，并研究有多少驱动蛋白一起工作，以创造更大的力量。