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

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-ter...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-02, Vol.117 (8), p.4061-4070
Main Authors: Yan, Liming, Qi, Yuanbo, Ricketson, Derek, Li, Lei, Subramanian, Kelly, Zhao, Jinghua, Yu, Caiting, Wu, Lijie, Sarsam, Reta, Wong, Melissa, Lou, Zhiyong, Rao, Zihe, Nunnari, Jodi, Hu, Junjie
Format: Article
Language:English
Subjects:
Assembly
Biological Sciences
Crystal structure
Dimers
Domains
Dynamin
Guanosine triphosphatases
Interfaces
Lipids
Membrane fusion
Membranes
Mitochondria
Structural analysis
Trimers
Yeasts
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1919116117