Structural highlights
FunctionEIF1_HUMAN Necessary for scanning and involved in initiation site selection. Promotes the assembly of 48S ribosomal complexes at the authentic initiation codon of a conventional capped mRNA. Publication Abstract from PubMedNonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain. Additionally, the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A accommodation. Structure-based experiments demonstrated the importance of decoding center interactions in all three coronaviruses and showed that the same regions of Nsp1 are necessary for the selective translation of viral RNAs. Our results provide a mechanistic framework to understand how Nsp1 controls preferential translation of viral RNAs. Universal features of Nsp1-mediated translational shutdown by coronaviruses.,Schubert K, Karousis ED, Ban I, Lapointe CP, Leibundgut M, Baumlin E, Kummerant E, Scaiola A, Schonhut T, Ziegelmuller J, Puglisi JD, Muhlemann O, Ban N Mol Cell. 2023 Oct 5;83(19):3546-3557.e8. doi: 10.1016/j.molcel.2023.09.002. PMID:37802027[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 14:11, 18 October 2023.