Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6

• Published in: Science (American Association for the Advancement of Science) Vol. 334; no. 6058; pp. 941 - 948
• Main Authors: Klinge, Sebastian, Voigts-Hoffmann, Felix, Leibundgut, Marc, Arpagaus, Sofia, Ban, Nenad
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 18.11.2011; The American Association for the Advancement of Science
• Subjects: active sites; Anti-Bacterial Agents - metabolism; Antibiotics; Base Sequence; Binding Sites; Biological and medical sciences; Crystal structure; Crystalline structure; Crystallization; Crystallography, X-Ray; cycloheximide; Cycloheximide - metabolism; Eukaryotes; Eukaryotic Initiation Factors - chemistry; Eukaryotic Initiation Factors - metabolism; Fundamental and applied biological sciences. Psychology; Models, Molecular; Molecular and cellular biology; Molecular biophysics; Molecular genetics; Molecular Sequence Data; Nucleic Acid Conformation; Peptide Chain Initiation, Translational; polypeptides; Protein Conformation; Protein Structure, Secondary; protein subunits; Protein synthesis; Proteins; Protozoan Proteins - chemistry; Protozoan Proteins - metabolism; RESEARCH ARTICLE; Ribonucleic acid; Ribosomal proteins; Ribosomal Proteins - chemistry; Ribosomal Proteins - metabolism; Ribosome Subunits, Large, Eukaryotic - chemistry; Ribosome Subunits, Large, Eukaryotic - metabolism; Ribosome Subunits, Large, Eukaryotic - ultrastructure; Ribosomes; RNA; RNA, Protozoan - chemistry; RNA, Protozoan - metabolism; RNA, Ribosomal - chemistry; RNA, Ribosomal - metabolism; RNA, Ribosomal, 5.8S - chemistry; RNA, Ribosomal, 5.8S - metabolism; Structure in molecular biology; Tetrahymena thermophila; Tetrahymena thermophila - chemistry; Tetrahymena thermophila - metabolism; Transfer RNA; Translation. Translation factors. Protein processing; Tunnels; Yeasts; Eukaryote; Ribosome; Subunit; Initiation; Crystalline structure
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1211204

Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymeno thermophila in complex with eukaryotic initiation factor 6 (elF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with elF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.