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1.A.117.  The Coronavirus Membrane Matrix-Protein (M-Protein) Family

The M-protein is the dominant organizing protein of the viral envelop, serving as the matrix structural protein (Fung and Liu 2018).  It is a component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with the other viral proteins, the Nucleocapsid (N-protein), the Spike (S-protein), the Envelope (E-protein), etc. (Rabaan et al. 2020)  It seems to have several functions. Mutations in its encoding gene allows it to functionally replace the 3a-protein viroporin (TC# 1.A.57), suggesting that the M-protein either has or can develop pore forming activity (Kuo and Masters 2010). Moreover, the sizes and topologies of these two proteins as well as the ORF 4a protein (TC# 1.A.89) are similar, with a transmembrane N-terminal half with three strongly hydrophobic TMSs and a C-terminal half that is largely hydrophilic.  Some of these proteins show 3 weakly hydrophobic peaks that may be transmembrane, but these characteristics apply to all three families, suggesting a relationship. (M. Saier, unpublished observations). The dynamics of membrane lipids and the integral M protein of SARS-CoV-2 enables it to better associate and aggregate only in a certain temperature range (i.e., ~ 30-40 degrees C) (Rath et al. 2022).


References associated with 1.A.117 family:

Barrantes, F.J. (2021). Structural biology of coronavirus ion channels. Acta Crystallogr D Struct Biol 77: 391-402. 33825700
Fung, T.S. and D.X. Liu. (2018). Post-translational modifications of coronavirus proteins: roles and function. Future Virol 13: 405-430. 32201497
Kuo, L. and P.S. Masters. (2010). Evolved variants of the membrane protein can partially replace the envelope protein in murine coronavirus assembly. J. Virol. 84: 12872-12885. 20926558
Rabaan, A.A., S.H. Al-Ahmed, S. Haque, R. Sah, R. Tiwari, Y.S. Malik, K. Dhama, M.I. Yatoo, D.K. Bonilla-Aldana, and A.J. Rodriguez-Morales. (2020). SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Infez Med 28: 174-184. 32275259
Rath, S.L., M. Tripathy, and N. Mandal. (2022). How Does Temperature Affect the Dynamics of SARS-CoV-2 M Proteins? Insights from Molecular Dynamics Simulations. J. Membr. Biol. 255: 341-356. 35552785
Shen, L., J.D. Bard, T.J. Triche, A.R. Judkins, J.A. Biegel, and X. Gai. (2021). Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications. Emerg Microbes Infect 10: 885-893. 33896413