title: Ribosomal protein L3: influence on ribosome structure and function.
abstract: Early studies demonstrated roles for ribosomal protein L3 in peptidyltransferase center formation and the ability of cells to propagate viruses. More recent studies have linked these two processes via the effects of mutants and drugs on programmed -1 ribosomal frameshifting. Here, we show that mutant forms of L3 result in ribosomes having increased affinities for both aminoacyl- and peptidyl-tRNAs. These defects potentiate the effects of sparsomycin, which promotes increased aminoalcyl-tRNA binding at the P-site, while antagonizing the effects anisomycin, a drug that promotes decreased peptidyl-tRNA binding at the A-site. The changes in ribosome affinities for tRNAs also correlate with decreased peptidyltransferase activities of mutant ribosomes, and with decreased rates of cell growth and protein synthesis. In vivo dimethylsulfate (DMS) protection studies reveal that small changes in L3 primary sequence also have significant effects on rRNA structure as far away as 100 A, supporting an allosteric model of ribosome function.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Petrov
authors.forename: Arturas
authors.initials: A
authors.lastname: Meskauskas
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
mesh_terms: D000495:Allosteric Site; D000841:Anisomycin / Q000494:pharmacology; D001483:Base Sequence; D005786:Gene Expression Regulation; D019614:Haloarcula marismortui / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012335:RNA, Ribosomal / Q000737:chemistry; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000737:chemistry*; D013033:Sparsomycin / Q000494:pharmacology; D013463:Sulfuric Acid Esters / Q000494:pharmacology
chemical_list: D012335:RNA, Ribosomal; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D013463:Sulfuric Acid Esters; D000841:Anisomycin; D013033:Sparsomycin; C007482:dimethyl sulfate