Illustration of a coronavirus virion in the respiratory mucosa, showing the positions of the four structural proteins and components of the extracellular environment.[15]
The M protein is the most abundant protein in coronavirus virions.[8][5][4] It is essential for viral replication.[4]
Viral assembly
The primary function of the M protein is organizing assembly of new virions.[4] It is involved in establishing viral shape and morphology. Individual M molecules interact with each other to form the viral envelope[7][9][8] and may be able to exclude host cell proteins from the viral membrane.[5] Studies of the SARS-CoV M protein suggest that M-M interactions involve both the N- and C-termini.[6] Coronaviruses are moderately pleomorphic and conformational variations of M appear to be associated with virion size.[5]
M forms protein-protein interactions with all three other major structural proteins.[4][7] M is necessary but not sufficient for viral assembly; M and the E protein expressed together are reportedly sufficient to form virus-like particles,[7] though some reports vary depending on experimental conditions and the specific virus studied.[6][13] In some reports M appears to be capable of inducing membrane curvature,[5] though others report M alone is insufficient for this and E is required.[7] Although the E protein is not necessarily essential, it appears to be required for normal viral morphology and may be responsible for establishing curvature or initiating viral budding.[7] M also appears to have functional roles in the later stages of viral maturation, secretion, and budding.[4]
Incorporation of the spike protein (S) - which is required for assembly of infectious virions - is reported to occur though M interactions and may depend on specific conformations of M.[5][13] The conserved amphipathic region C-terminal to the third transmembrane segment is important for spike interactions.[13] Interactions with M appear to be required for correct subcellular localization of S at the viral budding site.[12] M interacts directly with the nucleocapsid (N) protein without requiring the presence of RNA.[6] This interaction appears to occur primarily through both proteins' C-termini.[4]
Other recent research has identified that SAS-COV-2 membrane protein when treated on human PBMC's causes a significant increase in pro inflammatory mediators such as TNF and IL-6.[19] The effects of exogenous SARS-COV-2 membrane protein challenge in mice was also studied. In these studies, exogenous membrane protein treated intra nasally caused a significant increase in pulmonary inflammation in mice leading to histological changes within the lungs.[20]
A study of SARS-CoV-2 sequences collected during the COVID-19 pandemic found that missense mutations in the M gene were relatively uncommon and suggested it was under purifying selection.[22] Similar results have been described for broader population genetics analyses over a wider range of related viruses, finding that the sequences of M and several non-structural proteins in the coronavirus genome are most subject to evolutionary constraints.[23]
^Haystead, T., Lee, E., Cho, K., Gullickson, G., Hughes, P., Krafsur, G., ... & Scarneo, S. (2023). Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein. Scientific Reports, 13(1), 22873.
^Haystead, T., Lee, E., Cho, K., Gullickson, G., Hughes, P., Krafsur, G., ... & Scarneo, S. (2023). Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein. Scientific Reports, 13(1), 22873.
