Structural basis of mitochondrial receptor binding and constriction by DRP1

Article

关键词: DEPENDENT PROTEIN-KINASE;    CRYSTAL-STRUCTURE;    FUNCTIONAL-ANALYSIS;    UCSF CHIMERA;    FISSION;    MID51;    MID49;    MFF;    OLIGOMERIZATION;    FUSION;   

DOI  :  10.1038/s41586-018-0211-2

来源: SCIE

【 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.

【 授权许可】

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