8ppl
From Proteopedia
MERS-CoV Nsp1 bound to the human 43S pre-initiation complex
Structural highlights
FunctionEIF3K_HUMAN Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S preinitiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. 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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Categories: Homo sapiens | Large Structures | Baeumlin E | Ban I | Ban N | Karousis ED | Kummerant E | Lapointe CP | Leibundgut M | Muehlemann O | Puglisi JD | Scaiola A | Schoenhut T | Schubert K | Ziegelmueller J
