Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway.


We describe in this report the characterization of the recently discovered N-linked glycosylation locus of the human bacterial pathogen Campylobacter jejuni, the first such system found in a species from the domain Bacteria. We exploited the ability of this locus to function in Escherichia coli to demonstrate through mutational and structural analyses that variant glycan structures can be transferred onto protein indicating the relaxed specificity of the putative oligosaccharyltransferase PglB. Structural data derived from these variant glycans allowed us to infer the role of five individual glycosyltransferases in the biosynthesis of the N-linked heptasaccharide. Furthermore, we show that C. jejuni- and E. coli-derived pathways can interact in the biosynthesis of N-linked glycoproteins. In particular, the E. coli encoded WecA protein, a UDP-GlcNAc: undecaprenylphosphate GlcNAc-1-phosphate transferase involved in glycolipid biosynthesis, provides for an alternative N-linked heptasaccharide biosynthetic pathway bypassing the requirement for the C. jejuni-derived glycosyltransferase PglC. This is the first experimental evidence that biosynthesis of the N-linked glycan occurs on a lipid-linked precursor prior to transfer onto protein. These findings provide a framework for understanding the process of N-linked protein glycosylation in Bacteria and for devising strategies to exploit this system for glycoengineering.

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@article{Linton2005FunctionalAO, title={Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway.}, author={Dennis Linton and Nick Dorrell and Paul G. Hitchen and Saba Amber and Andrey V Karlyshev and Howard Morris and Anne Dell and Miguel A Valvano and Markus Aebi and Brendan W. Wren}, journal={Molecular microbiology}, year={2005}, volume={55 6}, pages={1695-703} }