title: The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination.
abstract: The ribosomal peptidyl transferase center is responsible for two fundamental reactions, peptide bond formation and nascent peptide release, during the elongation and termination phases of protein synthesis, respectively. We used in vitro genetics to investigate the functional importance of conserved 23S rRNA nucleotides located in the peptidyl transferase active site for transpeptidation and peptidyl-tRNA hydrolysis. While mutations at A2451, U2585, and C2063 (E. coli numbering) did not significantly affect either of the reactions, substitution of A2602 with C or its deletion abolished the ribosome ability to promote peptide release but had little effect on transpeptidation. This indicates that the mechanism of peptide release is distinct from that of peptide bond formation, with A2602 playing a critical role in peptide release during translation termination.
authors.affiliation: Center for Pharmaceutical Biotechnology-M/C 870, University of Illinois, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Polacek
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gomez
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
authors.forename: Liqun
authors.initials: L
authors.lastname: Xiong
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Alexander
authors.initials: A
authors.lastname: Mankin
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D008024:Ligands; D015394:Molecular Structure; D009154:Mutation; D009690:Nucleic Acid Conformation; D010443:Peptide Chain Termination, Translational; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000378:metabolism; D013824:Thermus / Q000737:chemistry / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D010455:Peptides; D012338:RNA, Ribosomal, 23S; D012346:RNA, Transfer, Amino Acyl; D012358:RNA, Transfer, Met; C024988:tRNA, formylmethionine-; D010458:Peptidyl Transferases