8t07

Publication Abstract from PubMed

The 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.