Molecular architecture of the autoinhibited kinesin-1 lambda particle.

Molecular architecture of the autoinhibited kinesin-1 lambda particle.
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DOI:
10.1126/sciadv.abp9660
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发表时间:
2022-09-16
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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尽管驱动蛋白酶机械化学不断取得进展,并且对货物识别机制的理解不断涌现,但尚不清楚这些功能如何由驱动蛋白序列的大部分成分编码的 α 螺旋卷曲线圈耦合和控制。在这里,我们将计算结构预测与单粒子负染色电子显微镜相结合,揭示了异四聚体驱动蛋白-1在致密状态下的卷曲螺旋结构。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-轻链界面与由先前被认为是折叠铰链的分子区域形成的四聚体组件紧密并置。这个自抑制框架需要揭示货物和其他调节因素的参与如何驱动驱动蛋白-1 激活。微管运动驱动蛋白-1 在其肘部折叠形成紧凑的自抑制 lambda 颗粒。
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 α-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 drives kinesin-1 activation. The microtubule motor kinesin-1 folds over at its elbow to form the compact autoinhibited lambda particle.
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发表时间: 2021-07-01
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