Subcellular localization of the enterobacterial common antigen GT-E-like glycosyltransferase, WecG

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2022

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Maczuga, N.
Tran, E.N.H.
Morona, R.

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Molecular Microbiology, 2022; 118(4):403-416

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Nicholas Maczuga, Elizabeth N. H. Tran, Renato Morona

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Enterobacterales have developed a specialized outer membrane polysaccharide (en-terobacterial common antigen [ECA]). ECA biosynthesis begins on the cytoplasmic side of the inner membrane (IM) where glycosyltransferases sequentially add sugar moieties to form a complete repeat unit which is then translocated across the IM by WzxE before being polymerized into short linear chains by WzyE/WzzE. Research into WecG, the enzyme responsible for generating ECA lipid-II, has not progressed beyond Barr et al. (1988) who described WecG as a membrane protein. Here we re-vise our understanding of WecG and re-characterize it as a peripherally associated membrane protein. Through the use of Western immunoblotting we show that WecG in Shigella flexneri is maintained to the IM via its three C-terminal helices and further identify key residues in helix II which are critical for this interaction which has allowed us to identify WecG as a GT-E glycosyltransferase. We investigate the possibility of protein complexes and ultimately show that ECA lipid-I maintains WecG to the mem-brane which is crucial for its function. This research is the first since Barr et al. (1988) to investigate the biochemistry of WecG and reveals possible novel drug targets to inhibit WecG and thus ECA function and cell viability.

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First published: 12 August 2022

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© 2022 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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