title: Mutations of highly conserved bases in the peptidyltransferase center induce compensatory rearrangements in yeast ribosomes.
abstract: Molecular dynamics simulation identified three highly conserved rRNA bases in the large subunit of the ribosome that form a three-dimensional (3D) "gate" that induces pausing of the aa-tRNA acceptor stem during accommodation into the A-site. A nearby fourth base contacting the "tryptophan finger" of yeast protein L3, which is involved in the coordinating elongation factor recruitment to the ribosome with peptidyltransfer, is also implicated in this process. To better understand the functional importance of these bases, single base substitutions as well as deletions at all four positions were constructed and expressed as the sole forms of ribosomes in yeast Saccharomyces cerevisiae. None of the mutants had strong effects on cell growth, translational fidelity, or on the interactions between ribosomes and tRNAs. However, the mutants did promote strong effects on cell growth in the presence of translational inhibitors, and differences in viability between yeast and Escherichia coli mutants at homologous positions suggest new targets for antibacterial therapeutics. Mutant ribosomes also promoted changes in 25S rRNA structure, all localized to the core of peptidyltransferase center (i.e., the proto-ribosome area). We suggest that a certain degree of structural plasticity is built into the ribosome, enabling it to ensure accurate translation of the genetic code while providing it with the flexibility to adapt and evolve.
authors: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.
authors: Rasa
authors: R
authors: Rakauskaite
authors: Jonathan D
authors: JD
authors: Dinman
mesh_terms: D001483:Base Sequence; D009154:Mutation; D009690:Nucleic Acid Conformation; D010458:Peptidyl Transferases / Q000235:genetics*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology*
chemical_list: D012335:RNA, Ribosomal; D010458:Peptidyl Transferases