| Structural highlights
Function
MGM1_YEAST Dynamin-related GTPase required for mitochondrial fusion. Coordinates interaction between the inner and outer mitochondrial membrane to promote the formation of the double membrane.[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.,Yan L, Qi Y, Ricketson D, Li L, Subramanian K, Zhao J, Yu C, Wu L, Sarsam R, Wong M, Lou Z, Rao Z, Nunnari J, Hu J Proc Natl Acad Sci U S A. 2020 Feb 10. pii: 1919116117. doi:, 10.1073/pnas.1919116117. PMID:32041880[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shepard KA, Yaffe MP. The yeast dynamin-like protein, Mgm1p, functions on the mitochondrial outer membrane to mediate mitochondrial inheritance. J Cell Biol. 1999 Feb 22;144(4):711-20. doi: 10.1083/jcb.144.4.711. PMID:10037792 doi:http://dx.doi.org/10.1083/jcb.144.4.711
- ↑ Wong ED, Wagner JA, Scott SV, Okreglak V, Holewinske TJ, Cassidy-Stone A, Nunnari J. The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion. J Cell Biol. 2003 Feb 3;160(3):303-11. PMID:12566426 doi:http://dx.doi.org/10.1083/jcb.200209015
- ↑ Herlan M, Vogel F, Bornhovd C, Neupert W, Reichert AS. Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J Biol Chem. 2003 Jul 25;278(30):27781-8. Epub 2003 Apr 21. PMID:12707284 doi:http://dx.doi.org/10.1074/jbc.M211311200
- ↑ Sesaki H, Jensen RE. Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J Biol Chem. 2004 Jul 2;279(27):28298-303. Epub 2004 Apr 14. PMID:15087460 doi:http://dx.doi.org/10.1074/jbc.M401363200
- ↑ Yan L, Qi Y, Ricketson D, Li L, Subramanian K, Zhao J, Yu C, Wu L, Sarsam R, Wong M, Lou Z, Rao Z, Nunnari J, Hu J. Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1. Proc Natl Acad Sci U S A. 2020 Feb 10. pii: 1919116117. doi:, 10.1073/pnas.1919116117. PMID:32041880 doi:http://dx.doi.org/10.1073/pnas.1919116117
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