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

点击翻译按钮获取中文摘要

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.