驱动蛋白
微管
有丝分裂
细胞生物学
小分子
生物物理学
生物
运动蛋白
分子马达
化学
生物化学
作者
Julia Locke,Agnel Praveen Joseph,Alejandro Peña,Martin M. Möckel,Thomas Mayer,Maya Topf,Carolyn A. Moores
标识
DOI:10.1073/pnas.1712169114
摘要
Significance Kinesins are a superfamily of ATP-dependent motors important for many microtubule-based functions, including multiple roles in mitosis. Small-molecule inhibitors of mitotic kinesins disrupt cell division and are being developed as antimitotic therapies. We investigated the molecular mechanism of the multitasking human mitotic kinesin Kif18A and its inhibition by the small molecule BTB-1. We used cryo-electron microscopy to visualize nucleotide-dependent conformational changes in microtubule-bound Kif18A, and the conformation of microtubule-bound, BTB-1-bound Kif18A. We calculated a putative BTB-1–binding site and validated this site experimentally to reveal the BTB-1 inhibition mechanism. Our work points to a general mechanism of kinesin inhibition, with wide implications for a targeted blockade of these motors in both dividing and interphase cells.
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