title: Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution.
abstract: Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 Å resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zürich, Zürich 8093, Switzerland.
authors.forename: Nick
authors.initials: N
authors.lastname: Quade
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zürich, Zürich 8093, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehringer
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zürich, Zürich 8093, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Leibundgut
authors.affiliation: Research Group Recombinant Protein Expression, Helmholtz Centre for Infection Research, Inhoffenstraße 7, Braunschweig 38124, Germany.
authors.forename: Joop
authors.initials: J
authors.lastname: van den Heuvel
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zürich, Zürich 8093, Switzerland.
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
mesh_terms: D001665:Binding Sites; D020285:Cryoelectron Microscopy; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000502:physiology*; D008958:Models, Molecular; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000502:physiology; D054682:Ribosome Subunits, Small, Eukaryotic / Q000502:physiology*
chemical_list: D000067556:Internal Ribosome Entry Sites; D012337:RNA, Ribosomal, 18S