Membrane topological model of glycosyltransferases of the GT-C superfamily

Albuquerque-Wendt, A. , Hütte, H. J., Buettner, F. F.R., Routier, F. H. and Baker, H. (2019) Membrane topological model of glycosyltransferases of the GT-C superfamily. International Journal of Molecular Sciences, 20(19), 4842. (doi: 10.3390/ijms20194842) (PMID:31569500) (PMCID:PMC6801728)

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Glycosyltransferases that use polyisoprenol-linked donor substrates are categorized in the GT-C superfamily. In eukaryotes, they act in the endoplasmic reticulum (ER) lumen and are involved in N-glycosylation, glypiation, O-mannosylation, and C-mannosylation of proteins. We generated a membrane topology model of C-mannosyltransferases (DPY19 family) that concurred perfectly with the 13 transmembrane domains (TMDs) observed in oligosaccharyltransferases (STT3 family) structures. A multiple alignment of family members from diverse organisms highlighted the presence of only a few conserved amino acids between DPY19s and STT3s. Most of these residues were shown to be essential for DPY19 function and are positioned in luminal loops that showed high conservation within the DPY19 family. Multiple alignments of other eukaryotic GT-C families underlined the presence of similar conserved motifs in luminal loops, in all enzymes of the superfamily. Most GT-C enzymes are proposed to have an uneven number of TDMs with 11 (POMT, TMTC, ALG9, ALG12, PIGB, PIGV, and PIGZ) or 13 (DPY19, STT3, and ALG10) membrane-spanning helices. In contrast, PIGM, ALG3, ALG6, and ALG8 have 12 or 14 TMDs and display a C-terminal dilysine ER-retrieval motif oriented towards the cytoplasm. We propose that all members of the GT-C superfamily are evolutionary related enzymes with preserved membrane topology.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Albuquerque-Wendt, Ms Andreia
Authors: Albuquerque-Wendt, A., Hütte, H. J., Buettner, F. F.R., Routier, F. H., and Baker, H.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:International Journal of Molecular Sciences
ISSN (Online):1422-0067
Published Online:29 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in International Journal of Molecular Sciences 20(19): 4842
Publisher Policy:Reproduced under a Creative Commons License

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