| Structural highlights
Function
MFN1_HUMAN Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN1 acts independently of the cytoskeleton. Overexpression induces the formation of mitochondrial networks.[1] [2] [3] [4]
Publication Abstract from PubMed
Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein. We show that the nucleotide-binding pocket is shallow and narrow, rendering weak hydrolysis and less dependence on magnesium ion, and that association of HB affects GTPase activity. MFN1 forms a dimer when GTP or GDP/BeF(3)(-), but not GDP or other analogs, is added. In addition, clustering of vesicles containing membrane-anchored MGD requires continuous GTP hydrolysis. These results suggest that MFN tethers apposing membranes, likely through nucleotide-dependent dimerization.
Structures of human mitofusin 1 provide insight into mitochondrial tethering.,Qi Y, Yan L, Yu C, Guo X, Zhou X, Hu X, Huang X, Rao Z, Lou Z, Hu J J Cell Biol. 2016 Dec 5;215(5):621-629. doi: 10.1083/jcb.201609019. PMID:27920125[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001 Mar;114(Pt 5):867-74. PMID:11181170
- ↑ Legros F, Lombes A, Frachon P, Rojo M. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol Biol Cell. 2002 Dec;13(12):4343-54. PMID:12475957 doi:http://dx.doi.org/10.1091/mbc.E02-06-0330
- ↑ Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci. 2003 Jul 1;116(Pt 13):2763-74. Epub 2003 May 20. PMID:12759376 doi:http://dx.doi.org/10.1242/jcs.00479
- ↑ Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem. 2013 Sep 20;288(38):27584-93. doi: 10.1074/jbc.M113.479873. Epub, 2013 Aug 6. PMID:23921378 doi:http://dx.doi.org/10.1074/jbc.M113.479873
- ↑ Qi Y, Yan L, Yu C, Guo X, Zhou X, Hu X, Huang X, Rao Z, Lou Z, Hu J. Structures of human mitofusin 1 provide insight into mitochondrial tethering. J Cell Biol. 2016 Dec 5;215(5):621-629. PMID:27920125 doi:10.1083/jcb.201609019
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