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Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-site of the Peptidyl Transferase Center

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Title: Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-site of the Peptidyl Transferase Center
Author(s): Ramu, Haripriya; Vazquez-Laslop, Nora; Klepacki, Dorota; Dai, Qing; Piccirilli, Joseph; Mankin, Alexander S.
Subject(s): nascent peptide structure ribosome
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.
Issue Date: 2011-02-04
Publisher: Elsevier (Cell Press)
Citation Info: Ramu, H., Vazquez-Laslop, N., Klepacki, D., Dai, Q., Piccirilli, J., Micura, R., & Mankin, A. S. 2011. Nascent Peptide in the ribosome exit tunnel affects functional properties of the a-site of the peptidyl transferase center. Molecular Cell. 41(3): 321-330. DOI: 10.1016/j.molcel.2010.12.031
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in Molecular Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Cell, [Vol 41, Issue 3, (February 4, 2011)] DOI: 10.1016/j.molcel.2010.12.031. The original publication is available at Post print version of article may differ from published version. The definitive version is available through Elsevier (Cell Press) at DOI: 10.1016/j.molcel.2010.12.031
ISSN: 1097-4164
Sponsor: This work was supported by grant MCB- 0824739 from the National Science Foundation (to ASM and NVL). QD was supported by the SPARK Award from the Chicago Biomedical Consortium.
Date Available in INDIGO: 2011-05-27

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