An Evolutionarily Conserved Strategy for Ribosome Binding and Host Translation Inhibition by β-coronavirus Non-structural Protein 1.

ABSTRACT: An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Non-structural protein 1 (Nsp1), which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-Coronaviruses (β-CoV) inhibits translation through ribosome binding. The C-terminal domain (CTD) of all β-CoV Nsp1s confers high-affinity ribosome binding despite low sequence conservation. Modeling of interactions of four Nsp1s with the ribosome identified the few absolutely conserved amino acids that, together with an overall conservation in surface charge, form the β-CoV Nsp1 ribosome-

SUBMITTER: Maurina SF 

PROVIDER: S-EPMC10543557 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature