Arginine-rhamnosylation as new strategy to activate translation elongation factor P

Jürgen Lassak; Eva C. Keilhauer; Maximilian Fürst; Kristin Wuichet; Julia Gödeke; Agata L. Starosta; Jhong Min Chen; Lotte Søgaard-Andersen; Jürgen Rohr; Daniel N. Wilson; Susanne Häussler; Matthias Mann; Kirsten Jung

doi:10.1038/nchembio.1751

Arginine-rhamnosylation as new strategy to activate translation elongation factor P

Jürgen Lassak, Eva C. Keilhauer, Maximilian Fürst, Kristin Wuichet, Julia Gödeke, Agata L. Starosta, Jhong Min Chen, Lotte Søgaard-Andersen, Jürgen Rohr, Daniel N. Wilson, Susanne Häussler, Matthias Mann, Kirsten Jung

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

Abstract

Ribosome stalling at polyproline stretches is common and fundamental. In bacteria, translation elongation factor P (EF-P) rescues such stalled ribosomes, but only when it is post-translationally activated. In Escherichia coli, activation of EF-P is achieved by (R)-Î 2-lysinylation and hydroxylation of a conserved lysine. Here we have unveiled a markedly different modification strategy in which a conserved arginine of EF-P is rhamnosylated by a glycosyltransferase (EarP) using dTDP-L-rhamnose as a substrate. This is to our knowledge the first report of N-linked protein glycosylation on arginine in bacteria and the first example in which a glycosylated side chain of a translation elongation factor is essential for function. Arginine-rhamnosylation of EF-P also occurs in clinically relevant bacteria such as Pseudomonas aeruginosa. We demonstrate that the modification is needed to develop pathogenicity, making EarP and dTDP-L-rhamnose-biosynthesizing enzymes ideal targets for antibiotic development.

Original language	English
Pages (from-to)	266-270
Number of pages	5
Journal	Nature Chemical Biology
Volume	11
Issue number	4
DOIs	https://doi.org/10.1038/nchembio.1751
State	Published - Apr 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

Funding

We would like to thank I. Weitl for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft: Center for Integrated Protein Science Munich (CiPSM; Exc114/2 to K.J. and WI3285/4-1 to D.N.W.) and the Max Planck Society (to E.C.K., K.W., L.S.-A. and M.M.). A.L.S. is funded by an AXA Research Fund Postdoctoral Fellowship. The work of S.H. and J.G. was supported by the Helmholtz Association and the Bundesministerium für Bildung und Forschung. J.-M.C. and J.R are funded by the US National Institutes of Health (CA 091901).

Funders	Funder number
National Institutes of Health (NIH)	CA 091901
National Institute of General Medical Sciences	R01GM105977
Deutsche Forschungsgemeinschaft	Exc114/2, WI3285/4-1
AXA Research Fund
Bundesministerium für Bildung und Forschung
Fritz-Haber-Institut der Max-Planck-Gesellschaft
Max Delbrück Center for Molecular Medicine in the Helmholtz Association

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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abstract = "Ribosome stalling at polyproline stretches is common and fundamental. In bacteria, translation elongation factor P (EF-P) rescues such stalled ribosomes, but only when it is post-translationally activated. In Escherichia coli, activation of EF-P is achieved by (R)-{\^I} 2-lysinylation and hydroxylation of a conserved lysine. Here we have unveiled a markedly different modification strategy in which a conserved arginine of EF-P is rhamnosylated by a glycosyltransferase (EarP) using dTDP-L-rhamnose as a substrate. This is to our knowledge the first report of N-linked protein glycosylation on arginine in bacteria and the first example in which a glycosylated side chain of a translation elongation factor is essential for function. Arginine-rhamnosylation of EF-P also occurs in clinically relevant bacteria such as Pseudomonas aeruginosa. We demonstrate that the modification is needed to develop pathogenicity, making EarP and dTDP-L-rhamnose-biosynthesizing enzymes ideal targets for antibiotic development.",

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Arginine-rhamnosylation as new strategy to activate translation elongation factor P

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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