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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 (M. Saier, unpublished observations).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).


This family belongs to the: Viroporin-2.

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
Zhang, Z., N. Nomura, Y. Muramoto, T. Ekimoto, T. Uemura, K. Liu, M. Yui, N. Kono, J. Aoki, M. Ikeguchi, T. Noda, S. Iwata, U. Ohto, and T. Shimizu. (2022). Structure of SARS-CoV-2 membrane protein essential for virus assembly. Nat Commun 13: 4399. 35931673