Title

Polyisoprenol Specificity in the Campylobacter Jejuni N-linked Glycosylation Pathway

Document Type

Article

Comments

Published by ACS Publications in Biochemistry Volume 46, pages 14342-14348

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Keywords

Campylobacter jejuni;PglB;PglC;PglJ;polyisoprene donor

Publisher

ACS Publications

Publication Source

Biochemistry

Abstract

Campylobacter jejuni contains a general N-linked glycosylation pathway in which a heptasaccharide is sequentially assembled onto a polyisoprenyl-diphosphate carrier and subsequently transferred to the asparagine side chain of an acceptor protein. The enzymes in the pathway function at a membrane interface and have in common amphiphilic membrane-bound polyisoprenyl-linked substrates. Herein we examine the potential role of the polyisoprene component of the substrates by investigating the relative substrate efficiencies of polyisoprene-modified analogs in individual steps in the pathway. Chemically defined substrates for PglC, PglJ and PglB are prepared via semisynthetic approaches. The substrates included polyisoprenols of varying length, double bond geometry, and degree of saturation to probe the role of the hydrophobic polyisoprene in substrate specificity. Kinetic analysis reveals that all three enzymes exhibit distinct preferences for the polyisoprenol carrier whereby cis-double bond geometry and α-unsaturation of the native substrate are important features, while the precise polyisoprene length may be less critical. These finding suggest that the polyisoprenol carrier plays a specific role in the function of these enzymes beyond a purely physical role as a membrane anchor. These studies underscore the potential of the C. jejuni N-linked glycosylation pathway as a system for investigating the biochemical and biophysical roles of polyisoprenol carriers common to prokaryotic and eukaryotic glycosylation.

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