驱动蛋白结构与运动机制  

Structures and Mechanisms of Kinesin's Walking

作　　者：曹添亮[1,2] 韩孟之 徐骥[1] 任瑛[1] 

机构地区：[1]中国科学院过程工程研究所多相复杂系统国家重点实验室,北京100190 [2]中国科学院大学,北京100049

出　　处：《中国生物化学与分子生物学报》2016年第7期734-744,共11页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.91434104)~~

摘　　要：驱动蛋白是一类能够利用ATP水解释放的化学能驱动其所携带的"货物"分子沿着微管(microtubule,MT)定向运动的分子马达,在细胞器运输、有丝分裂、轴突运输等方面有着重要的生理作用。随着驱动蛋白结合ADP、ATP和未结合核苷酸(APO)三种特征状态的晶体结构的解析,驱动蛋白构象变化的研究得到了进一步发展,而在力产生机制和运动模型方面仍然存在较大争议。本文以kinesin-1家族为例,分析了驱动蛋白三种特征状态结构的特点、状态结构间的构象转变,论述了驱动蛋白的力产生机制和整个迈步过程。并探讨了驱动蛋白的运动模型,同时采用分子动力学模拟比较了驱动蛋白的两种迈步方式,为深入研究驱动蛋白提供了一定的理论计算。最后,基于本课题组对复杂体系的研究,对驱动蛋白体系的控制机制提出了新的假设,并对未来的研究方向进行了展望。Kinesin is a superfamily of microtubule-based molecular motor protein,which directionally transports various cargoes obtaining energy through hydrolyzing ATP molecules;and plays very important roles in organelles transport,mitosis and axonal transport,etc.After the crystal structures of three characteristic states of kinesin systems have been solved,namely,ADP,ATP,and APO（no nucleotide）states.The studies on the structural changes among these characteristic states have been promoted.However,the mechanisms of the directional walking of kinesin have not been unveiled yet,including the molecular details of the force generation（whether the head-neck linker docking will contribute to the force generation）,the walking pattern（whether kinesin moves by a ＂hand-over-hand ＂ or an＂inchworm＂）.Here,we take kinesin-1 family as example,summarize the progress on the directional walking of kinesin-1,including the molecular details of the characteristic states,the structural changes among them,the force generation mechanism,the possible pathway of kinesin walking,and the patterns of kinesin walking.Furthermore,we studied two different models of kinesin walking by atomic scale models with molecular dynamics simulations methods.Our simulation results demonstrated that kinesin prefers to move forward from left or right side rather than move over the motor head,and the structural changes in ATP cycle establish a framework for understanding the conversion of chemical energy into mechanical work.Finally,based on our previous study of complex systems,namely the evolution of complex systems are always governed by compromise of competition between two or more differentdominant mechanisms,possible walking mechanism of kinesin is prospected.

关 键 词：驱动蛋白 分子马达 微管 分子动力学模拟 控制机制 

分 类 号：Q6[生物学—生物物理学]