Synergistic autoinhibition and activation mechanisms control kinesin-1 motor activity.
Synergistic autoinhibition and activation mechanisms control kinesin-1 motor activity.
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DOI：
10.1016/j.celrep.2022.110900
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发表时间：
2022-05-31
期刊：
影响因子：
8.8
通讯作者：
McKenney, Richard J.
中科院分区：
文献类型：
--
作者：
Chiba, Kyoko;Ori-McKenney, Kassandra M.;Niwa, Shinsuke;McKenney, Richard J.
Kinesin-1 活性受自身抑制调节。驱动蛋白重链 (KHC) 内的分子内相互作用被认为是运动调节的一方面。 KHC 还与驱动蛋白轻链 (KLC) 结合，后者与运动的自动抑制和激活有关。我们表明，KLC 抑制驱动蛋白-微管相互作用，独立于 KHC 内提出的分子内相互作用。结合 KLC 的货物适配器蛋白刺激了持续运动，但激活的驱动蛋白复合物的着陆率仍然很低。微管相关蛋白 7 (MAP7) 通过增加激活的驱动蛋白马达的着陆率和运行长度来增强运动性。我们的结果支持一个模型，即驱动蛋白的运动活性受到协同抑制机制的调节，并且与 KLC 结合的货物适配器释放这两种机制。然而，激活运动的稳健微管关联需要非运动 MAP。因此，人驱动蛋白受到协同自抑制和激活机制的调节。驱动蛋白-1 (KIF5) 沿着微管运输货物。 KIF5 运动的机制已被了解，但运动如何自动抑制和激活仍不清楚。千叶等人。报告了 KIF5 四聚体的协同自抑制和激活，并表明这些过程领域的主要模型需要修订。
Kinesin-1 activity is regulated by autoinhibition. Intramolecular interactions within the kinesin heavy chain (KHC) are proposed to be one facet of motor regulation. The KHC also binds to the kinesin light chain (KLC), which has been implicated in both autoinhibition and activation of the motor. We show that the KLC inhibits the kinesin-microtubule interaction independently from the proposed intramolecular interaction within KHC. Cargo-adaptor proteins that bind the KLC stimulated processive movement, but the landing rate of activated kinesin complexes remained low. Microtubule-associated protein 7 (MAP7) enhanced motility by increasing the landing rate and run length of the activated kinesin motors. Our results support a model whereby the motor activity of the kinesin is regulated by synergistic inhibition mechanisms and that cargo-adaptor binding to the KLC releases both mechanisms. However, a non-motor MAP is required for robust microtubule association of the activated motor. Thus, human kinesin is regulated by synergistic autoinhibition and activation mechanisms. Kinesin-1 (KIF5) transports cargo along microtubules. The mechanism of KIF5 movement is understood, but how the motor is autoinhibited and activated remains unclear. Chiba et al. report both synergistic autoinhibition and activation of the KIF5 tetramer and suggest that predominant models in the field for these processes need revision.
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影响因子：
16.8
作者：
通讯作者：
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DOI：
10.1126/science.1254198
发表时间：
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期刊：
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期刊：
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发表时间：
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期刊：
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DOI：
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发表时间：
2006-05-22
期刊：
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影响因子：
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通讯作者：
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