8T05

Structure of Ciona Myomaker bound to Fab1A1

Summary for 8T05

• Entry DOI: 10.2210/pdb8t05/pdb
• EMDB information: 40935
• Descriptor: Myomaker, 1A1 Fab heavy chain, 1A1 Fab light chain, ... (6 entities in total)
• Functional Keywords: membrane protein
• Biological source: Ciona robusta; More
• Total number of polymer chains: 4
• Total formula weight: 76448.60

Authors

Long, T.,Li, X. (deposition date: 2023-05-31, release date: 2023-09-27, Last modification date: 2024-11-13)

Primary citation

Long, T.,Zhang, Y.,Donnelly, L.,Li, H.,Pien, Y.C.,Liu, N.,Olson, E.N.,Li, X.
Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion.
Nat.Struct.Mol.Biol., 30:1746-1754, 2023

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 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.

PubMed: 37770716
DOI: 10.1038/s41594-023-01110-8

Experimental method

ELECTRON MICROSCOPY (3.22 Å)