Structure of the hepatitis C virus IRES bound to the human 80S ribosome: remodeling of the HCV IRES.
Initiation of translation of the hepatitis C virus (HCV) polyprotein is driven by an internal ribosome entry site (IRES) RNA that bypasses much of the eukaryotic translation initiation machinery. Here, single-particle electron cryomicroscopy has been used to study the mechanism of HCV IRES-mediated initiation. A HeLa in vitro translation system was used to assemble human IRES-80S ribosome complexes under near physiological conditions; these were stalled before elongation. Domain 2 of the HCV IRES is bound to the tRNA exit site, touching the L1 stalk of the 60S subunit, suggesting a mechanism for the removal of the HCV IRES in the progression to elongation. Domain 3 of the HCV IRES positions the initiation codon in the ribosomal mRNA binding cleft by binding helix 28 at the head of the 40S subunit. The comparison with the previously published binary 40S-HCV IRES complex reveals structural rearrangements in the two pseudoknot structures of the HCV IRES in translation initiation.
Boehringer
Daniel
D
Max Planck Institute for Biophysical Chemistry, 3D Electron Cryomicroscopy, Am Fassberg 11, 37077 Göttingen, Germany.
Thermann
Rolf
R
Ostareck-Lederer
Antje
A
Lewis
Joe D
JD
Stark
Holger
H
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002846:Chromatography, Affinity; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics*; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014031:Tobramycin / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D021122:Protein Subunits; D012367:RNA, Viral; D012269:Ribosomal Proteins; C041308:ribosomal protein S40; C039913:ribosomal protein S80; D014031:Tobramycin