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TitleStructural basis for regulated assembly of the mitochondrial fission GTPase Drp1.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 1328, Year 2024
Publish dateFeb 13, 2024
AuthorsKristy Rochon / Brianna L Bauer / Nathaniel A Roethler / Yuli Buckley / Chih-Chia Su / Wei Huang / Rajesh Ramachandran / Maria S K Stoll / Edward W Yu / Derek J Taylor / Jason A Mears /
PubMed AbstractMitochondrial fission is a critical cellular event to maintain organelle function. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 ...Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the mechanisms that regulate correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intramolecular rearrangements to achieve the assembly-competent state observed in previous structures. This structural insight provides understanding into the mechanism for regulated self-assembly of the mitochondrial fission machinery.
External linksNat Commun / PubMed:38351080 / PubMed Central
MethodsEM (single particle)
Resolution5.97 Å
Structure data

40967

8t1h

EMDB-40967, PDB-8t1h:
Cryo-EM structure of a full-length, native Drp1 dimer
Method: EM (single particle) / Resolution: 5.97 Å

Source
  • homo sapiens (human)
KeywordsCYTOSOLIC PROTEIN / Dynamin-related protein 1 / Drp1 / mitochondrial fission / GTPase

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