Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 8, Pages 4061-4070Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1919116117
Keywords
membrane fusion; mitochondria; dynamin; inner membrane; structure
Categories
Funding
- National Key Research and Development Program [2016YFA0500201, 2017YFC0840302, 2017YFC0840300]
- National Natural Science Foundation of China [91854202, 31630020, 3170040488]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB39000000]
- NIH [R37GM097432, R01GM126081]
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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.
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