Allosteric control of the ribosome by small-molecule antibiotics Journal Article
| Authors: | Wang, L.; Pulk, A.; Wasserman, M. R.; Feldman, M. B.; Altman, R. B.; Doudna Cate, J. H.; Blanchard, S. C. |
| Article Title: | Allosteric control of the ribosome by small-molecule antibiotics |
| Abstract: | Protein synthesis is targeted by numerous, chemically distinct antibiotics that bind and inhibit key functional centers of the ribosome. Using single-molecule imaging and X-ray crystallography, we show that the aminoglycoside neomycin blocks aminoacyl-transfer RNA (aa-tRNA) selection and translocation as well as ribosome recycling by binding to helix 69 (H69) of 23S ribosomal RNA within the large subunit of the Escherichia coli ribosome. There, neomycin prevents the remodeling of intersubunit bridges that normally accompanies the process of subunit rotation to stabilize a partially rotated ribosome configuration in which peptidyl (P)-site tRNA is constrained in a previously unidentified hybrid position. Direct measurements show that this neomycin-stabilized intermediate is incompatible with the translation factor binding that is required for distinct protein synthesis reactions. These findings reveal the functional importance of reversible intersubunit rotation to the translation mechanism and shed new light on the allosteric control of ribosome functions by small-molecule antibiotics. © 2012 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; fluorescence; anti-bacterial agents; protein synthesis; escherichia coli; protein biosynthesis; binding site; models, molecular; crystallography, x-ray; rna, ribosomal; x ray crystallography; drug protein binding; rna transport; escherichia coli proteins; rna, transfer, amino acyl; rna, bacterial; allosterism; neomycin; ribosome; aminoacyl transfer rna; ribosome subunits, large, bacterial; ribosome subunits, small, bacterial |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 19 |
| Issue: | 9 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-09-01 |
| Start Page: | 957 |
| End Page: | 963 |
| Language: | English |
| DOI: | 10.1038/nsmb.2360 |
| PUBMED: | 22902368 |
| PROVIDER: | scopus |
| PMCID: | PMC3645490 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 28 January 2013" - "CODEN: NSMBC" - "Source: Scopus" |
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