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TitleStructural basis of mitochondrial receptor binding and constriction by DRP1.
Journal, issue, pagesNature, Vol. 558, Issue 7710, Page 401-405, Year 2018
Publish dateJun 13, 2018
AuthorsRaghav Kalia / Ray Yu-Ruei Wang / Ali Yusuf / Paul V Thomas / David A Agard / Janet M Shaw / Adam Frost /
PubMed AbstractMitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the ...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.
External linksNature / PubMed:29899447 / PubMed Central
MethodsEM (helical sym.)
Resolution4.22 Å
Structure data

8874

5wp9

EMDB-8874, PDB-5wp9:
Structural Basis of Mitochondrial Receptor Binding and Constriction by Dynamin-Related Protein 1
Method: EM (helical sym.) / Resolution: 4.22 Å

Chemicals

ChemComp-GCP:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-PCP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Mitochondrial division / Dynamin related-protein-1 / Nucleotide / MID49

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