Gene

Protein–protein interaction

Coronavirus

Cell biology

Membrane protein

Biology

Viral replication

Virology

Receptor

Biochemistry

Protein structure

Vesicle-associated membrane protein 8

Coronavirus disease 2019 (COVID-19)

Viral structural protein

Organic chemistry

Membrane

Viral matrix protein

Viral entry

Protein domain

Infectious disease (medical specialty)

Viral protein

Dimer

Medicine

Chemistry

Virus

Transmembrane domain

Biophysics

Transmembrane protein

Disease

Pathology

Nature Communications

The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and morphogenesis. However, the process of M protein-driven virus assembly are largely unknown. Here, we report the cryo-electron microscopy 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. M protein further assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is unexpectedly similar to SARS-CoV-2 ORF3a, a viral ion channel. Moreover, the 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. Our data shed light on the M protein-driven virus assembly mechanism and provide a structural basis for therapeutic intervention targeting M protein.

Structure of SARS-CoV-2 membrane protein essential for virus assembly