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TitleCryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 11, Page 1746-1754, Year 2023
Publish dateSep 28, 2023
AuthorsTao Long / Yichi Zhang / Linda Donnelly / Hui Li / Yu-Chung Pien / Ning Liu / Eric N Olson / Xiaochun Li /
PubMed AbstractThe 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 linksNat Struct Mol Biol / PubMed:37770716
MethodsEM (single particle)
Resolution2.72 - 3.38 Å
Structure data

40933

8t03

EMDB-40933, PDB-8t03:
Structure of mouse Myomaker bound to Fab18G7 in detergent
Method: EM (single particle) / Resolution: 2.72 Å

40934

8t04

EMDB-40934, PDB-8t04:
Structure of mouse Myomaker bound to Fab18G7 in nanodiscs
Method: EM (single particle) / Resolution: 2.98 Å

40935

8t05

EMDB-40935, PDB-8t05:
Structure of Ciona Myomaker bound to Fab1A1
Method: EM (single particle) / Resolution: 3.22 Å

40936

8t06

EMDB-40936, PDB-8t06:
Structure of mouse Myomaker mutant-R107A bound to Fab18G7
Method: EM (single particle) / Resolution: 3.32 Å

40937

8t07

EMDB-40937, PDB-8t07:
Structure of mouse Myomaker mutant-Y118A bound to Fab18G7
Method: EM (single particle) / Resolution: 3.38 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CLR:
CHOLESTEROL

ChemComp-LBN:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / phospholipid*YM

ChemComp-HOH:
WATER

Source
  • mus musculus (house mouse)
  • ciona robusta (invertebrata)
KeywordsMEMBRANE PROTEIN

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