한빛사 논문
Junhong Choi1,2,4,6, James Marks3,5,6, Jingji Zhang1, Dong-Hua Chen1, Jinfan Wang1, Nora Vázquez-Laslop3,*, Alexander S. Mankin3,* and Joseph D. Puglisi1,*
1 Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
2 Department of Applied Physics, Stanford University, Stanford, CA, USA.
3 Center for Biomolecular Sciences, University of Illinois, Chicago, IL, USA.
4 Present address: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
5 Present address: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
6 These authors contributed equally: Junhong Choi, James Marks
*Correspondence to Nora Vázquez-Laslop or Alexander S. Mankin or Joseph D. Puglisi
Abstract
Chloramphenicol (CHL) and linezolid (LZD) are antibiotics that inhibit translation. Both were thought to block peptide-bond formation between all combinations of amino acids. Yet recently, a strong nascent peptide context-dependency of CHL- and LZD-induced translation arrest was discovered. Here we probed the mechanism of action of CHL and LZD by using single-molecule Förster resonance energy transfer spectroscopy to monitor translation arrest induced by antibiotics. The presence of CHL or LZD does not substantially alter dynamics of protein synthesis until the arrest-motif of the nascent peptide is generated. Inhibition of peptide-bond formation compels the fully accommodated A-site transfer RNA to undergo repeated rounds of dissociation and nonproductive rebinding. The glycyl amino-acid moiety on the A-site Gly-tRNA manages to overcome the arrest by CHL. Our results illuminate the mechanism of CHL and LZD action through their interactions with the ribosome, the nascent peptide and the incoming amino acid, perturbing elongation dynamics.
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