title: An accuracy center in the ribosome conserved over 2 billion years.
abstract: The accuracy of translation in Escherichia coli is profoundly influenced by three interacting ribosomal proteins, S12, S4, and S5. Mutations at lysine-42 of S12, originally isolated as causing resistance to streptomycin, increase accuracy. Countervailing "ribosomal ambiguity mutations" (ram) in S4 or S5 decrease accuracy. In the eukaryotic ribosome of Saccharomyces cerevisiae, mutations in SUP46 and SUP44, encoding the proteins equivalent to S4 and S5, lead to omnipotent suppression--i.e., to less accurate translation. The evolution of ribosomal protein S12 can be traced, by comparison with archaebacteria and Tetrahymena, to S28 of S. cerevisiae, even though the two proteins share only very limited regions of homology. However, one region that has been conserved contains a lysine residue whose mutation leads to increased accuracy in E. coli. We have introduced into S28 of yeast the same amino acid substitutions that led to the original streptomycin-resistant mutations in E. coli. We find that they have a profound effect on the accuracy of translation and interact with SUP44 and SUP46, just as predicted from the E. coli model. Thus, the interplay of these three proteins to provide the optimal level of accuracy of translation has been conserved during the 2 billion years of evolution that separate E. coli from S. cerevisiae.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: L E
authors.initials: LE
authors.lastname: Alksne
authors.forename: R A
authors.initials: RA
authors.lastname: Anthony
authors.forename: S W
authors.initials: SW
authors.lastname: Liebman
authors.forename: J R
authors.initials: JR
authors.lastname: Warner
mesh_terms: D004247:DNA; D004926:Escherichia coli / Q000235:genetics; D016153:Genes, Suppressor; D008969:Molecular Sequence Data; D010303:Paromomycin / Q000494:pharmacology; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D012270:Ribosomes / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013307:Streptomycin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D012269:Ribosomal Proteins; D010303:Paromomycin; D004247:DNA; D013307:Streptomycin