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Title | Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 11, Page 1746-1754, Year 2023 |
Publish date | Sep 28, 2023 |
Authors | Tao Long / Yichi Zhang / Linda Donnelly / Hui Li / Yu-Chung Pien / Ning Liu / Eric N Olson / Xiaochun Li / |
PubMed Abstract | 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 ...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. |
External links | Nat Struct Mol Biol / PubMed:37770716 |
Methods | EM (single particle) |
Resolution | 2.72 - 3.38 Å |
Structure data | EMDB-40933, PDB-8t03: EMDB-40934, PDB-8t04: EMDB-40935, PDB-8t05: EMDB-40936, PDB-8t06: EMDB-40937, PDB-8t07: |
Chemicals | ChemComp-ZN: ChemComp-CLR: ChemComp-LBN: ChemComp-HOH: |
Source |
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Keywords | MEMBRANE PROTEIN |