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

Nature Chemical Biology, 2015, doi:10.1038/nchembio.1751, published on 16.02.2015
Nature Chemical Biology, online article
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)-β-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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