C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation.
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