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 (M. Saier, unpublished observations).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.



Barrantes, F.J. (2021). Structural biology of coronavirus ion channels. Acta Crystallogr D Struct Biol 77: 391-402.

Fung, T.S. and D.X. Liu. (2018). Post-translational modifications of coronavirus proteins: roles and function. Future Virol 13: 405-430.

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.

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.

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.

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.

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.


TC#NameOrganismal TypeExample

Matrix (M)-protein (putative viroporin) of 217 aas with 3 closely spaced TMSs in the N-terminal half of the protein.

M-protein of Guangdong chinese water skink coronavirus


Membrane glycoprotein of 222 aas and 3 or 4 TMSs. It is a component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins. However, it may also function a viroporin, Orf3a (Barrantes 2021). Variants of the M protein arise with high frequency, suggesting that these mutants are more biologically fit, perhaps related to glucose uptake during viral replication (Shen et al. 2021). Zhang et al. 2022 reported the cryo-EM structure of the SARS-CoV-2 M protein in two different conformations. M protein forms a mushroom-shaped dimer, composed of two transmembrane domain-swapped three-helix bundles and two intravirion domains. It also assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is similar to SARS-CoV-2 ORF3a, a viroporin (TC# 1.A.57.1.5). Interaction analyses of M protein with nucleocapsid protein (N) and RNA suggest that the M protein mediates the concerted recruitment of these components through the positively charged intravirion domain (Zhang et al. 2022).


M-protein of severe acute respiratory syndrome coronavirus 2, SARS CoV2.


M-protein of 268 aas and 3 N-terminal TMSs

M protein of Common moorhen coronavirus HKU21


Membrane matrix (M) glycoprotein of 261 aas and 3 strongly hydrophobic TMSs in the N-terminal half of the protein, preceded by a single N-terminal TMS (possibly a targetting signal sequence), followed by a relatively hydrophilic C-terminal half that includes 3 weakly hydrophobic peaks that could be transmembrane but probably are not.  These properties are characteristic of many but not all of the members of this family, including members of both sub-families, 1.A.57.1 and 1.A. 57.2.

M-protein of the transmissible gastroenteritis virus (TGEV)


Matrix (M) protein of 219 aas and 3 N-terminal TMSs.

M protein (MERS) of betacoronavirus England 1


Membrane (M)-protein of 275 aas and 3 (+ 2 or 3 possible) TMSs

M-protein of Bottlenose dolphin coronavirus


M-protein, or "M" of 225 aas and 3 TMSs. It is a component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins.

M of Avian infectious bronchitis virus (strain DE072) (IBV)