Myomesin-1 is a protein that in humans is encoded by the MYOM1gene.[5][6] Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the thick filament. Embryonic forms of Myomesin-1 have been detected in dilated cardiomyopathy.
Structure
Alternatively spliced variants of MYOM1, including EH-myomesin,[7] Skelemin[8] and Myomesin-1[8][9][10] have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues.[8] Myomesin-1, like myomesin 2 and titin, is a member of a family of myosin-associated proteins containing structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that it has intermediate filament core-like motifs, one near each terminus.[11] Myomesin-1 and Myomesin-2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. Alternatively spliced, tissue-specific transcript variants encoding different isoforms have been identified.[12] Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.[13]
Function
Titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to Myomesin-1 and myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link myofibrils with the intermediate filamentcytoskeleton.[11] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[14] Myomesin-1 functions to mediate stretch-induced signaling,[15] and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity.[16]
Clinical Significance
The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of dilated cardiomyopathy, coincident with isoform switches in titin.[17]
MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a.[18]
Interactions
Skelemin/Myomesin-1 has been shown to interact with:
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Speel EJ, van der Ven PF, Albrechts JC, Ramaekers FC, Fürst DO, Hopman AH (Nov 1998). "Assignment of the human gene for the sarcomeric M-band protein myomesin (MYOM1) to 18p11.31-p11.32". Genomics. 54 (1): 184–6. doi:10.1006/geno.1998.5503. PMID9806852.
^ abcSteiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89. doi:10.1006/geno.1998.5682. PMID10036188.
^Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98. doi:10.1016/j.jmb.2004.10.040. PMID15571722.
^Reddy KB, Fox JE, Price MG, Kulkarni S, Gupta S, Das B, Smith DM (2008). "Nuclear localization of Myomesin-1: possible functions". Journal of Muscle Research and Cell Motility. 29 (1): 1–8. doi:10.1007/s10974-008-9137-x. PMID18521710. S2CID12298270.
^Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79. doi:10.1016/j.jmb.2005.03.055. PMID15890201.
^Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S (Sep 2011). "Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1". Genes to Cells. 16 (9): 961–72. doi:10.1111/j.1365-2443.2011.01542.x. PMID21794030. S2CID3272510.
Vinkemeier U, Obermann W, Weber K, Fürst DO (Sep 1993). "The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin-associated proteins". Journal of Cell Science. 106 (1): 319–30. doi:10.1242/jcs.106.1.319. PMID7505783.
Obermann WM, Plessmann U, Weber K, Fürst DO (Oct 1995). "Purification and biochemical characterization of myomesin, a myosin-binding and titin-binding protein, from bovine skeletal muscle". European Journal of Biochemistry. 233 (1): 110–5. doi:10.1111/j.1432-1033.1995.110_1.x. PMID7588733.
Steiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89. doi:10.1006/geno.1998.5682. PMID10036188.
Porter JD, Merriam AP, Gong B, Kasturi S, Zhou X, Hauser KF, Andrade FH, Cheng G (Sep 2003). "Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle". The Journal of Experimental Biology. 206 (Pt 17): 3101–12. doi:10.1242/jeb.00511. PMID12878677. S2CID21867785.
Hornemann T, Kempa S, Himmel M, Hayess K, Fürst DO, Wallimann T (Sep 2003). "Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein". Journal of Molecular Biology. 332 (4): 877–87. doi:10.1016/S0022-2836(03)00921-5. PMID12972258.
Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98. doi:10.1016/j.jmb.2004.10.040. PMID15571722.
Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79. doi:10.1016/j.jmb.2005.03.055. PMID15890201.
