Multiple Roles of SARS-CoV-2 N Protein Facilitated by Proteoform-Specific Interactions with RNA, Host Proteins, and Convalescent Antibodies.

ABSTRACT: The SARS-CoV-2 nucleocapsid (N) protein is a highly immunogenic viral protein that plays essential roles in replication and virion assembly. Here, using native mass spectrometry, we show that dimers are the functional unit of ribonucleoprotein assembly and that N protein binds RNA with a preference for GGG motifs, a common motif in coronavirus packaging signals. Unexpectedly, proteolytic processing of N protein resulted in the formation of additional proteoforms. The N-terminal proteoforms bind RNA, with the same preference for GGG motifs, and bind to cyclophilin A, an interaction which can be abolished by approved immunosuppressant cyclosporin A. Furthermore, N proteoforms showed significantly different interactions with IgM, IgG, and IgA antibodies from convalescent plasma. Notably, the

SUBMITTER: Lutomski CA 

PROVIDER: S-EPMC8231660 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature