8t06
From Proteopedia
Structure of mouse Myomaker mutant-R107A bound to Fab18G7
Structural highlights
FunctionMYMK_MOUSE Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers (PubMed:23868259, PubMed:28386024, PubMed:28681861, PubMed:30197239). Actively participates in the membrane fusion reaction by mediating the mixing of cell membrane lipids (hemifusion) upstream of MYMX (PubMed:30197239). Acts independently of MYMX (PubMed:30197239). Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers (PubMed:25085416). Also involved in skeletal muscle hypertrophy, probably by mediating the fusion of satellite cells with myofibers (PubMed:28186492).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe fusion of mononucleated myoblasts produces multinucleated muscle fibers leading to the formation of skeletal muscle. Myomaker, a skeletal muscle-specific membrane protein, is essential for myoblast fusion. Here we report the cryo-EM structures of mouse Myomaker (mMymk) and Ciona robusta Myomaker (cMymk). Myomaker contains seven transmembrane helices (TMs) that adopt a G-protein-coupled receptor-like fold. TMs 2-4 form a dimeric interface, while TMs 3 and 5-7 create a lipid-binding site that holds the polar head of a phospholipid and allows the alkyl tails to insert into Myomaker. The similarity of cMymk and mMymk suggests a conserved Myomaker-mediated cell fusion mechanism across evolutionarily distant species. Functional analyses demonstrate the essentiality of the dimeric interface and the lipid-binding site for fusogenic activity, and heterologous cell-cell fusion assays show the importance of transcellular interactions of Myomaker protomers for myoblast fusion. Together, our findings provide structural and functional insights into the process of myoblast fusion. Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion.,Long T, Zhang Y, Donnelly L, Li H, Pien YC, Liu N, Olson EN, Li X Nat Struct Mol Biol. 2023 Nov;30(11):1746-1754. doi: 10.1038/s41594-023-01110-8. , Epub 2023 Sep 28. PMID:37770716[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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