title: Crystal structure of an RNA tertiary domain essential to HCV IRES-mediated translation initiation.
abstract: The hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA drives internal initiation of viral protein synthesis during host cell infection. In the tertiary structure of the IRES RNA, two helical junctions create recognition sites for direct binding of the 40S ribosomal subunit and eukaryotic initiation factor 3 (eIF3). The 2.8 A resolution structure of the IIIabc four-way junction, which is critical for binding eIF3, reveals how junction nucleotides interact with an adjacent helix to position regions directly involved in eIF3 recognition. Two of the emergent helices stack to form a nearly continuous A-form duplex, while stacking of the other two helices is interrupted by the insertion of junction residues into the helix minor groove. This distorted stack probably serves as an important recognition surface for the translational machinery.
authors.affiliation: [1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114 USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520-8114 USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kieft
authors.forename: Kaihong
authors.initials: K
authors.lastname: Zhou
authors.forename: Angie
authors.initials: A
authors.lastname: Grech
authors.forename: Ronald
authors.initials: R
authors.lastname: Jubin
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D005814:Genes, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000235:genetics / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational; D010448:Peptide Initiation Factors / Q000378:metabolism; D039665:Prokaryotic Initiation Factor-3; D011485:Protein Binding; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009711:Nucleotides; D010448:Peptide Initiation Factors; D039665:Prokaryotic Initiation Factor-3; D012367:RNA, Viral; D014764:Viral Proteins