8T1H

Cryo-EM structure of a full-length, native Drp1 dimer

Summary for 8T1H

• Entry DOI: 10.2210/pdb8t1h/pdb
• EMDB information: 40967
• Descriptor: Dynamin-1-like protein (1 entity in total)
• Functional Keywords: dynamin-related protein 1, drp1, mitochondrial fission, gtpase, cytosolic protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 163968.19

Authors

Rochon, K.,Mears, J.A. (deposition date: 2023-06-02, release date: 2024-02-21, Last modification date: 2024-05-01)

Primary citation

Rochon, K.,Bauer, B.L.,Roethler, N.A.,Buckley, Y.,Su, C.C.,Huang, W.,Ramachandran, R.,Stoll, M.S.K.,Yu, E.W.,Taylor, D.J.,Mears, J.A.
Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1.
Nat Commun, 15:1328-1328, 2024

PubMed Abstract: 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.

PubMed: 38351080
DOI: 10.1038/s41467-024-45524-4

Experimental method

ELECTRON MICROSCOPY (5.97 Å)