Structure of SARS-CoV-2 membrane protein essential for virus assembly
Zhikuan Zhang, Norimichi Nomura, Yukiko Muramoto, Toru Ekimoto, Tomoko Uemura, Kehong Liu, Moeko Yui, Nozomu Kono, Junken Aoki, Mitsunori Ikeguchi, Takeshi Noda, So Iwata, Umeharu Ohto, Toshiyuki Shimizu
Abstract
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.