University of Oulu

Fawzi Khoder-Agha, Deborah Harrus, Guillaume Brysbaert, Marc F. Lensink, Anne Harduin-Lepers, Tuomo Glumoff, Sakari Kellokumpu, Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains, Journal of Biological Chemistry, Volume 294, Issue 39,2019, Pages 14383-14393, ISSN 0021-9258,

Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains : molecular interactions between B4GALT1 and ST6GAL1

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Author: Khoder-Agha, Fawzi1; Harrus, Deborah1; Brysbaert, Guillaume2;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7A, 90220 Oulu, Finland
2Université de Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.6 MB)
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Language: English
Published: , 2019
Publish Date: 2021-10-11


β-1,4-Galactosyltransferase 1 (B4GALT1) and ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) catalyze the successive addition of terminal β-1,4–linked galactose and α-2,6–linked sialic acid to N-glycans. Their exclusive interaction in the Golgi compartment is a prerequisite for their full catalytic activity, whereas a lack of this interaction is associated with cancers and hypoxia. To date, no structural information exists that shows how glycosyltransferases functionally assemble with each other. Using molecular docking simulations to predict interaction surfaces, along with mutagenesis screens and high-throughput FRET analyses in live cells to validate these predictions, we show here that B4GALT1 and ST6GAL1 interact via highly charged noncatalytic surfaces, leaving the active sites exposed and accessible for donor and acceptor substrate binding. Moreover, we found that the assembly of ST6GAL1 homomers in the endoplasmic reticulum before ST6GAL1 activation in the Golgi utilizes the same noncatalytic surface, whereas B4GALT1 uses its active-site surface for assembly, which silences its catalytic activity. Last, we show that the homomeric and heteromeric B4GALT1/ST6GAL1 complexes can assemble laterally in the Golgi membranes without forming cross-cisternal contacts between enzyme molecules residing in the opposite membranes of each Golgi cisterna. Our results provide detailed mechanistic insights into the regulation of glycosyltransferase interactions, the transitions between B4GALT1 and ST6GAL1 homo- and heteromers in the Golgi, and cooperative B4GALT1/ST6GAL1 function in N-glycan synthesis.

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Volume: 294
Issue: 39
Pages: 14383 - 14393
DOI: 10.1074/jbc.RA119.009539
Type of Publication: A1 Journal article – refereed
Copyright information: ©2019 The Authors, Creative Commons, This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article. To request permission for a type of use not listed, please contact Elsevier Global Rights Department.