8t03

Structure of mouse Myomaker bound to Fab18G7 in detergentStructure of mouse Myomaker bound to Fab18G7 in detergent

Structural highlights

8t03 is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.72Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MYMK_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 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^[7]

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

References

↑ Millay DP, O'Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R, Olson EN. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature. 2013 Jul 18;499(7458):301-5. PMID:23868259 doi:10.1038/nature12343
↑ Millay DP, Sutherland LB, Bassel-Duby R, Olson EN. Myomaker is essential for muscle regeneration. Genes Dev. 2014 Aug 1;28(15):1641-6. PMID:25085416 doi:10.1101/gad.247205.114
↑ Goh Q, Millay DP. Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy. Elife. 2017 Feb 10;6:e20007. PMID:28186492 doi:10.7554/eLife.20007
↑ Bi P, Ramirez-Martinez A, Li H, Cannavino J, McAnally JR, Shelton JM, Sánchez-Ortiz E, Bassel-Duby R, Olson EN. Control of muscle formation by the fusogenic micropeptide myomixer. Science. 2017 Apr 21;356(6335):323-327. PMID:28386024 doi:10.1126/science.aam9361
↑ Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan WM, Webb BD, Robson CD, Cheng L, Van Ryzin C, Ramirez-Martinez A, Mohassel P, Leppert M, Scholand MB, Grunseich C, Ferreira CR, Hartman T, Hayes IM, Morgan T, Markie DM, Fagiolini M, Swift A, Chines PS, Speck-Martins CE, Collins FS, Jabs EW, Bönnemann CG, Olson EN, Carey JC, Robertson SP, Manoli I, Engle EC. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 Jul 6;8:16077. PMID:28681861 doi:10.1038/ncomms16077
↑ Leikina E, Gamage DG, Prasad V, Goykhberg J, Crowe M, Diao J, Kozlov MM, Chernomordik LV, Millay DP. Myomaker and Myomerger Work Independently to Control Distinct Steps of Membrane Remodeling during Myoblast Fusion. Dev Cell. 2018 Sep 24;46(6):767-780.e7. PMID:30197239 doi:10.1016/j.devcel.2018.08.006
↑ Long T, Zhang Y, Donnelly L, Li H, Pien YC, Liu N, Olson EN, Li X. Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion. Nat Struct Mol Biol. 2023 Nov;30(11):1746-1754. PMID:37770716 doi:10.1038/s41594-023-01110-8

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OCA

[1] Millay DP, O'Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R, Olson EN. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature. 2013 Jul 18;499(7458):301-5. PMID:23868259 doi:10.1038/nature12343

[2] Millay DP, Sutherland LB, Bassel-Duby R, Olson EN. Myomaker is essential for muscle regeneration. Genes Dev. 2014 Aug 1;28(15):1641-6. PMID:25085416 doi:10.1101/gad.247205.114

[3] Goh Q, Millay DP. Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy. Elife. 2017 Feb 10;6:e20007. PMID:28186492 doi:10.7554/eLife.20007

[4] Bi P, Ramirez-Martinez A, Li H, Cannavino J, McAnally JR, Shelton JM, Sánchez-Ortiz E, Bassel-Duby R, Olson EN. Control of muscle formation by the fusogenic micropeptide myomixer. Science. 2017 Apr 21;356(6335):323-327. PMID:28386024 doi:10.1126/science.aam9361

[5] Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan WM, Webb BD, Robson CD, Cheng L, Van Ryzin C, Ramirez-Martinez A, Mohassel P, Leppert M, Scholand MB, Grunseich C, Ferreira CR, Hartman T, Hayes IM, Morgan T, Markie DM, Fagiolini M, Swift A, Chines PS, Speck-Martins CE, Collins FS, Jabs EW, Bönnemann CG, Olson EN, Carey JC, Robertson SP, Manoli I, Engle EC. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 Jul 6;8:16077. PMID:28681861 doi:10.1038/ncomms16077

[6] Leikina E, Gamage DG, Prasad V, Goykhberg J, Crowe M, Diao J, Kozlov MM, Chernomordik LV, Millay DP. Myomaker and Myomerger Work Independently to Control Distinct Steps of Membrane Remodeling during Myoblast Fusion. Dev Cell. 2018 Sep 24;46(6):767-780.e7. PMID:30197239 doi:10.1016/j.devcel.2018.08.006

[7] Long T, Zhang Y, Donnelly L, Li H, Pien YC, Liu N, Olson EN, Li X. Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion. Nat Struct Mol Biol. 2023 Nov;30(11):1746-1754. PMID:37770716 doi:10.1038/s41594-023-01110-8

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