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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Cis-acting resistance peptides reveal dual ribosome inhibitory action of the macrolide josamycin
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. (ehrenberg)
Institute of Technology, University of Tartu, Tartu, Estonia.
Institute of Technology, University of Tartu, Tartu, Estonia.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. (ehrenberg)
Show others and affiliations
2009 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 91, no 8, 989-995 p.Article in journal (Refereed) Published
Abstract [en]

Macrolide antibiotics block the entrance of nascent peptides to the peptide exit tunnel of the large ribosomal subunit. Expression of specific cis-acting peptides confers low-level macrolide-resistance. We show that, in the case of josamycin, peptide expression does not eject josamycin from the ribosome, implying a peptide resistance mechanism different from that previously suggested for erythromycin. We find dipeptide formation and dipeptidyl-tRNA drop-off in the presence of josamycin to be much slower during translation of resistance than of control mRNAs. We demonstrate low-level josamycin resistance by over-expression of peptidyl-tRNA hydrolase. These findings suggest dual growth-inhibitory action of josamycin by (i) direct inhibition of peptide-elongation and (ii) indirect inhibition of peptide-elongation through rapid peptidyl-tRNA drop-off, leading to depletion of tRNA isoacceptors available for protein synthesis. We propose that josamycin resistance peptide expression brings ribosomes into a "quarantine" state with small drop-off rate, thereby eliminating the josamycin dependent depletion of tRNA isoacceptors in the protein-synthesis-active state.

Place, publisher, year, edition, pages
2009. Vol. 91, no 8, 989-995 p.
Keyword [en]
Macrolide, Josamycin, Protein synthesis, Inhibition, Resistance
National Category
Biological Sciences
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-104046DOI: 10.1016/j.biochi.2009.05.002ISI: 000268530700006PubMedID: 19463886OAI: oai:DiVA.org:uu-104046DiVA: diva2:219295
Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Molecular Biology
In the same journal
Biochimie
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 421 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf