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arXiv 0710.4558cond-mat.softcond-mat.stat-mechq-bio.BM
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驱动蛋白马达定向步进动力学的机械控制

Mechanical control of the directional stepping dynamics of the kinesin motor

Changbong Hyeon, José N. Onuchic

摘要:

在构成驱动蛋白的机械化学循环的多个步骤中,当驱动蛋白从一个微管(MT)结合位点移动到另一个微管结合位点时,观察到最有趣的事件之一。然而,在相对较短的时间尺度(~100微秒)内发生的步进运动超出了当前实验的分辨率,因此仍然缺乏对8 nm步长内的实时动态的基本理解。例如,动力冲程(或构象变化)的速率,导致颈连接器的未对接到对接的转变,是未知的,并且在8纳米步骤期间存在的子步骤仍然是驱动蛋白社区中有争议的问题。通过使用明确的结构的驱动蛋白二聚体和MT组成的13个原丝(PF),我们研究了步进动力学与功率冲程(kp)的变化率。我们估计1/kp <~ 20微秒以避免平均时间轨迹中的子步。对于1/kp>20微秒的缓慢动力冲程,平均时间迹线显示出暗示瞬态中间体存在的子步,这让人想起最近的高分辨率单分子实验。我们确定中间体的构象中,拴系的头部被困在旁边的结合位点的相邻PF。我们还发现了一个部分展开(开裂)的结合基序发生在过渡态合奏之前的驱动蛋白和MT之间的结合途径。

英文摘要:

Among the multiple steps constituting the kinesin's 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 (~100 microsec) 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 (PFs), we study the stepping dynamics with varying rates of power stroke (kp). We estimate that 1/kp <~ 20 microsec to avoid a substep in an averaged time trace. For a slow power stroke with 1/kp>20 microsec, 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 PF. We also find a partial unfolding (cracking) of the binding motifs occurring at the transition state ensemble along the pathways prior to binding between the kinesin and MT.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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