Nonstructural protein 1 (nsp1) is a coronavirus (CoV) virulence factor that restricts cellular gene expression by inhibiting translation through blocking the mRNA entry channel of the 40S ribosomal subunit and by promoting mRNA degradation. We perform a detailed structure-guided mutational analysis of SARS-CoV-2 nsp1, revealing insight into how it coordinates these activities against host but not viral mRNA. We find that residues in the N-terminal and central regions of nsp1 not involved in docking into the 40S mRNA entry channel nonetheless stabilize its association with the ribosome and mRNA, both enhancing its restriction of host gene expression and enabling mRNA containing the SARS-CoV-2 leader sequence to escape translational repression. These data support a model in which viral mRNA binding functionally alters the association of nsp1 with the ribosome, which has implications for drug targeting and understanding how engineered or emerging mutations in SARS-CoV-2 nsp1 could attenuate the virus.
Many students share the common belief
that the limiting reactant
in a chemical reaction is the reactant in the smallest quantity of
material. To help students overcome this difficulty a hands-on activity
for the limiting reactant concept was developed. The activity incorporates
the three levels of representation (macroscopic, submicroscopic, and
symbolic) and allows students to make connections among them by directly
working at three stations. Each station incorporates one level of
representation allowing students to explore one level of representation
at a time. The focus of the activity is to help students understand
thoroughly the topic of limiting reactant, including concepts related
to it, such as reaction stoichiometry.
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