文章基本信息

标题：Mechanical control of the directional stepping dynamics of the kinesin motor
本地全文：下载
作者：Changbong Hyeon ; José N. Onuchic
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2007
卷号：104
期号：44
页码：17382-17387
DOI：10.1073/pnas.0708828104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Among the multiple steps constituting the kinesin mechanochemical cycle, one of the most interesting events is observed when kinesins move an 8-nm step from one microtubule (MT)-binding site to another. The stepping motion that occurs within a relatively short time scale ({approx}100 {micro}s) is, however, beyond the resolution of current experiments. Therefore, a basic understanding to the real-time dynamics within the 8-nm step is still lacking. For instance, the rate of power stroke (or conformational change) that leads to the undocked-to-docked transition of neck-linker is not known, and the existence of a substep during the 8-nm step still remains a controversial issue in the kinesin community. By using explicit structures of the kinesin dimer and the MT consisting of 13 protofilaments, we study the stepping dynamics with varying rates of power stroke (kp). We estimate that k[IMG]f1.gif" ALT="Formula" BORDER="0"> [lsim] 20 {micro}s to avoid a substep in an averaged time trace. For a slow power stroke with k[IMG]f1.gif" ALT="Formula" BORDER="0"> > 20 {micro}s, the averaged time trace shows a substep that implies the existence of a transient intermediate, which is reminiscent of a recent single-molecule experiment at high resolution. We identify the intermediate as a conformation in which the tethered head is trapped in the sideway binding site of the neighboring protofilament. We also find a partial unfolding (cracking) of the binding motifs occurring at the transition state ensemble along the pathways before binding between the kinesin and MT.
关键词：cracking ; neck-linker zippering ; power stroke ; rectified diffusion