Weijman Johannes F, Yadav Sathish K N, Surridge Katherine J, Cross Jessica A, Borucu Ufuk, Mantell Judith, Woolfson Derek N, Schaffitzel Christiane, Dodding Mark P
School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Sci Adv. 2022 Sep 16;8(37):eabp9660. doi: 10.1126/sciadv.abp9660.
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.
尽管驱动蛋白酶的机械化学不断取得进展，并且对货物识别机制的认识也在不断深入，但尚不清楚这些功能是如何由驱动蛋白蛋白质序列的一大部分所编码的α-螺旋卷曲螺旋进行耦合和控制的。在这里，我们将计算结构预测与单颗粒负染色电子显微镜相结合，以揭示处于紧凑状态的异源四聚体驱动蛋白-1的卷曲螺旋结构。支架中的一个不寻常的弯曲使得复合物能够折叠，使驱动蛋白重链-轻链界面与由分子中先前被认为是折叠铰链的区域形成的四聚体组装紧密并置。这种自抑制框架对于揭示货物和其他调节因子的结合如何驱动驱动蛋白-1的激活是必需的。
