The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load.
The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load.
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DOI：
10.1016/j.cub.2015.03.013
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发表时间：
2015-05-04
期刊：
影响因子：
9.2
通讯作者：
Block, Steven M.
中科院分区：
文献类型：
--
作者：
Andreasson, Johan O. L.;Shastry, Shankar;Hancock, William O.;Block, Steven M.
运动蛋白对外部负载的反应是其团队工作能力的基础，并决定了货物运输的净速度和方向性。哺乳动物驱动蛋白-2 (KIF3A/B) 是一种异源三聚体马达，参与神经元中鞭毛内运输和囊泡运动。已知双向货物运输是由与同一货物结合的 KIF3A/B 和动力蛋白的相反活性引起的，但对驱动蛋白-2 的负载依赖性特性知之甚少。我们使用反馈控制的光陷阱来探测小鼠 KIF3A/B 在各种负载和核苷酸条件下的速度、运行长度和解结合动力学。 kinesin-2 电机速度对外力的敏感度低于 kinesin-1，但其持续性随着负载而急剧下降，并且偶尔会观察到电机滑动和重新连接。通过研究同源二聚体结构来表征每个运动域，并且对数据的全局拟合产生了量化主要力依赖性动力学转变的综合途径。 KIF3A/B 异二聚体的特性介于两个同二聚体之间，并且独特的负载依赖性行为可归因于运动域的特性，而不是颈连接子或卷曲螺旋茎。我们得出结论，KIF3A/B 的力依赖性运动与传统的驱动蛋白-1 显着不同。对抗相反的动力蛋白力，KIF3A/B 马达预计会快速解开和重新结合，从而导致与驱动蛋白-1 性质不同的运输行为。
The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains, and not to the neck-linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.
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DOI：
10.1126/science.1204824
发表时间：
2011-08-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kaan HY;Hackney DD;Kozielski F
通讯作者：
Kozielski F
影响因子：
21.3
作者：
Schnitzer, MJ;Visscher, K;Block, SM
通讯作者：
Block, SM
DOI：
10.1073/pnas.0436709100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Block, SM;Asbury, CL;Lang, MJ
通讯作者：
Lang, MJ
DOI：
10.1073/pnas.1107841108
发表时间：
2011-11-22
影响因子：
11.1
作者：
Kunwar, Ambarish;Tripathy, Suvranta K.;Gross, Steven P.
通讯作者：
Gross, Steven P.
影响因子：
4.8
作者：
Rosenfeld, SS;Fordyce, PM;Block, SM
通讯作者：
Block, SM