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From Proteopedia
Structural basis for GTP hydrolysis and conformational change of mitofusin 1 in mediating mitochondrial fusion
Structural highlights
FunctionMFN1_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 PubMedFusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF3(-). The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF3(-) (GDP-BeF3(-)). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion. The proposed model is supported by results from in vitro biochemical assays and mitochondria morphology rescue assays in MFN1-deleted cells. These findings offer an explanation for how Charcot-Marie-Tooth neuropathy type 2 A (CMT2A)-causing mutations compromise MFN-mediated fusion. Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion.,Yan L, Qi Y, Huang X, Yu C, Lan L, Guo X, Rao Z, Hu J, Lou Z Nat Struct Mol Biol. 2018 Mar;25(3):233-243. doi: 10.1038/s41594-018-0034-8. Epub, 2018 Feb 26. PMID:29483649[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Huang X | Qi Y | Yan L | Yu C
