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...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 117; no. 8; pp. 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 Journal Article
LanguageEnglish
Published United States National Academy of Sciences 25.02.2020
Subjects
Assembly
Biological Sciences
Crystal structure
Dimers
Domains
Dynamin
Guanosine triphosphatases
Interfaces
Lipids
Membrane fusion
Membranes
Mitochondria
Structural analysis
Trimers
Yeasts
inner membrane
mitochondria
structure
dynamin
membrane fusion
Online AccessGet full text

Cover

More Information
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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
1L.Y., Y.Q., and D.R. contributed equally to this work.
Reviewers: J.E.H., National Institutes of Health; and T.J.P., Indian Institute of Science Education and Research.
Author contributions: L.Y., Y.Q., D.R., K.S., J.N., and J.H. designed research; L.Y., Y.Q., D.R., L.L., K.S., J.Z., C.Y., L.W., R.S., and M.W. performed research; D.R., K.S., Z.L., Z.R., J.N., and J.H. analyzed data; and J.N. and J.H. wrote the paper.
Contributed by Jodi Nunnari, January 16, 2020 (sent for review November 4, 2019; reviewed by Jenny E. Hinshaw and Thomas John Pucadyil)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1919116117