Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26155016.
- Also identified by DOI 10.1038/ncomms8646 and PMC identifier 4510694.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cryoelectron Microscopy
- Hepacivirus
- Internal Ribosome Entry Sites
- Ribosome Subunits, Small, Eukaryotic