Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1

Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4061-4070. doi: 10.1073/pnas.1919116117. Epub 2020 Feb 10.


The fusion of inner mitochondrial membranes requires dynamin-like GTPases, Mgm1 in yeast and OPA1 in mammals, but how they mediate membrane fusion is poorly understood. Here, we determined the crystal structure of Saccharomyces cerevisiae short Mgm1 (s-Mgm1) in complex with GDP. It revealed an N-terminal GTPase (G) domain followed by two helix bundles (HB1 and HB2) and a unique C-terminal lipid-interacting stalk (LIS). Dimers can form through antiparallel HB interactions. Head-to-tail trimers are built by intermolecular interactions between the G domain and HB2-LIS. Biochemical and in vivo analyses support the idea that the assembly interfaces observed here are native and critical for Mgm1 function. We also found that s-Mgm1 interacts with negatively charged lipids via both the G domain and LIS. Based on these observations, we propose that membrane targeting via the G domain and LIS facilitates the in cis assembly of Mgm1, potentially generating a highly curved membrane tip to allow inner membrane fusion.

Keywords: dynamin; inner membrane; membrane fusion; mitochondria; structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray*
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Guanosine Diphosphate / chemistry*
  • Guanosine Diphosphate / metabolism
  • Lipid Metabolism
  • Membrane Fusion
  • Mitochondria / enzymology*
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • MGM1 protein, S cerevisiae
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • Guanosine Diphosphate
  • GTP-Binding Proteins

Associated data

  • PDB/6JSJ