caa a22 4500 528785869 20190713030955.0 cr unu---uuuuu 180924s2015 xx s 000 0 eng 10.3929/ethz-b-000103868 doi 10.1038/ncomms8646 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/103868 Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-angstrom resolution [Elektronische Daten] [Nick Quade, Daniel Boehringer, Marc Leibundgut, Joop Van den Heuvel, Nenad Ban] Nat Commun Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Quade Nick joint author Boehringer Daniel joint author Leibundgut Marc joint author Van den Heuvel Joop joint author Ban Nenad joint author Nature Communications London : Nature Publishing Group 6, p. 7646 2041-1723 http://hdl.handle.net/20.500.11850/103868 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/103868 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Quade Nick joint author ETHRESEARCH 700 1- Boehringer Daniel joint author ETHRESEARCH 700 1- Leibundgut Marc joint author ETHRESEARCH 700 1- Van den Heuvel Joop joint author ETHRESEARCH 700 1- Ban Nenad joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 6, p. 7646 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access