title: Nascent peptide in the ribosome exit tunnel affects functional properties of the A-site of the peptidyl transferase center.
abstract: The ability to monitor the nascent peptide structure and to respond functionally to specific nascent peptide sequences is a fundamental property of the ribosome. An extreme manifestation of such response is nascent peptide-dependent ribosome stalling, involved in the regulation of gene expression. The molecular mechanisms of programmed translation arrest are unclear. By analyzing ribosome stalling at the regulatory cistron of the antibiotic resistance gene ermA, we uncovered a carefully orchestrated cooperation between the ribosomal exit tunnel and the A-site of the peptidyl transferase center (PTC) in halting translation. The presence of an inducing antibiotic and a specific nascent peptide in the exit tunnel abrogate the ability of the PTC to catalyze peptide bond formation with a particular subset of amino acids. The extent of the conferred A-site selectivity is modulated by the C-terminal segment of the nascent peptide, where the third-from-last residue plays a critical role.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607, USA.
authors.forename: Haripriya
authors.initials: H
authors.lastname: Ramu
authors.forename: Nora
authors.initials: N
authors.lastname: Vázquez-Laslop
authors.forename: Dorota
authors.initials: D
authors.lastname: Klepacki
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Joseph
authors.initials: J
authors.lastname: Piccirilli
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mankin
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055162:Biocatalysis; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010458:Peptidyl Transferases; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D008780:Methyltransferases; C431709:ErmA protein, Bacteria; D010458:Peptidyl Transferases