Molecular architecture of the autoinhibited kinesin-1 lambda particle
Molecular architecture of the autoinhibited kinesin-1 lambda particle
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DOI：
10.1101/2022.04.28.489841
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发表时间：
2022-04
期刊：
影响因子：
13.6
通讯作者：
Johannes F. Weijman;Sathish K. N. Yadav;K. Surridge;Jessica A. Cross;Ufuk Borucu;J. Mantell;D. Woolfson;C. Schaffitzel;M. P. Dodding
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文献类型：
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作者：
Johannes F. Weijman;Sathish K. N. Yadav;K. Surridge;Jessica A. Cross;Ufuk Borucu;J. Mantell;D. Woolfson;C. Schaffitzel;M. P. Dodding
尽管在驱动蛋白酶机械化学和新兴的货物识别机制的理解不断取得进展，它是不知道这些功能是如何耦合和控制的α-螺旋卷曲螺旋编码的驱动蛋白蛋白序列的大部分。在这里，我们结合联合收割机计算结构预测与单粒子负染电子显微镜，揭示了卷曲螺旋结构的异源四聚体驱动蛋白-1，在其紧凑的状态。支架中不寻常的弯曲使得复合物能够折叠，使驱动蛋白重链-轻链界面与由先前假定为折叠铰链的分子区域形成的四聚体组装体紧密并置。需要这个自动抑制的框架来揭示货物和其他调节因子的参与如何驱动驱动蛋白-1激活。总结声明集成的计算结构预测与电子显微镜揭示了卷曲螺旋结构的自抑制紧凑型构象的微管马达，驱动蛋白-1。
Despite continuing progress in kinesin enzyme mechanochemistry and emerging understanding of the cargo recognition machinery, it is not known how these functions are coupled and controlled by the alpha-helical coiled coils encoded by a large component of kinesin protein sequences. Here, we combine computational structure prediction with single-particle negative stain electron microscopy to reveal the coiled-coil architecture of heterotetrameric kinesin-1, in its compact state. An unusual flexion in the scaffold enables folding of the complex, bringing the kinesin heavy chain-light chain interface into close apposition with a tetrameric assembly formed from the region of the molecule previously assumed to be the folding hinge. This framework for autoinhibition is required to uncover how engagement of cargo and other regulatory factors drive kinesin-1 activation. Summary statement Integration of computational structure prediction with electron microscopy reveals the coiled-coil architecture of the autoinhibited compact conformer of the microtubule motor, kinesin-1.