GTP酶
线粒体分裂
生物物理学
线粒体
生物
细胞生物学
蛋白质丝
生物化学
作者
Raghav Kalia,Ray Yau Wang,Ali Yusuf,Paul G. Thomas,David A. Agard,Janet M. Shaw,Adam Frost
出处
期刊:Nature
[Springer Nature]
日期:2018-06-13
卷期号:558 (7710): 401-405
被引量:168
标识
DOI:10.1038/s41586-018-0211-2
摘要
Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery.
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