title: Role of antibiotic ligand in nascent peptide-dependent ribosome stalling.
abstract: Specific nascent peptides in the ribosome exit tunnel can elicit translation arrest. Such ribosome stalling is used for regulation of expression of some bacterial and eukaryotic genes. The stalling is sensitive to additional cellular cues, most commonly the binding of specific small-molecular-weight cofactors to the ribosome. The role of cofactors in programmed translation arrest is unknown. By analyzing nascent peptide- and antibiotic-dependent ribosome stalling that controls inducible expression of antibiotic resistance genes in bacteria, we have found that the antibiotic is directly recognized as a part of the translation modulating signal. Even minute structural alterations preclude it from assisting in ribosome stalling, indicating the importance of precise molecular interactions of the drug with the ribosome. One of the sensors that monitor the structure of the antibiotic is the 23S rRNA residue C2610, whose mutation reduces the efficiency of nascent peptide- and antibiotic-dependent ribosome stalling. These findings establish a new paradigm of the role of the cofactor in programmed translation arrest in which a small molecule is recognized along with specific nascent peptide sequences as a composite structure that provokes arrest of translation. A similar mechanism could be used by the ribosome to sense a variety of cellular metabolites.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Illinois, 900 South Ashland Avenue, Chicago, IL 60607, USA. nvazquez@uic.edu
authors.forename: Nora
authors.initials: N
authors.lastname: Vázquez-Laslop
authors.forename: Dorota
authors.initials: D
authors.lastname: Klepacki
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Mulhearn
authors.forename: Haripriya
authors.initials: H
authors.lastname: Ramu
authors.forename: Olga
authors.initials: O
authors.lastname: Krasnykh
authors.forename: Scott
authors.initials: S
authors.lastname: Franzblau
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mankin
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002474:Cell-Free System; D008024:Ligands; D018942:Macrolides / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism*; D014176:Protein Biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D008024:Ligands; D018942:Macrolides; D010455:Peptides