uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The Impact of Aminoglycosides on the Dynamics of Translation Elongation
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Show others and affiliations
2013 (English)In: Cell Reports, ISSN 2211-1247, Vol. 3, no 2, 497-508 p.Article in journal (Refereed) Published
Abstract [en]

Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally distinct aminoglycosides that bind to the aminoacyl-transfer RNA site (A site) in the prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin. Using several single-molecule fluorescence measurements combined with structural and biochemical techniques, we observed distinct changes to translational dynamics for each aminoglycoside. While all three drugs effectively inhibit translation elongation, their actions are structurally and mechanistically distinct. Apramycin does not displace A1492 and A1493 at the decoding center, as demonstrated by a solution nuclear magnetic resonance structure, causing only limited miscoding; instead, it primarily blocks translocation. Paromomycin and gentamicin, which displace A1492 and A1493, cause significant miscoding, block intersubunit rotation, and inhibit translocation. Our results show the power of combined dynamics, structural, and biochemical approaches to elucidate the complex mechanisms underlying translation and its inhibition.

Place, publisher, year, edition, pages
2013. Vol. 3, no 2, 497-508 p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-206764DOI: 10.1016/j.celrep.2013.01.027ISI: 000321895200022OAI: oai:DiVA.org:uu-206764DiVA: diva2:645383
Available from: 2013-09-04 Created: 2013-09-04 Last updated: 2014-02-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Johansson, MagnusEhrenberg, Måns
By organisation
Structure and Molecular BiologyDepartment of Cell and Molecular Biology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 204 hits
ReferencesLink to record
Permanent link

Direct link