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

The Journal of Biological Chemistry
Fawzi Khoder-AghaSakari Kellokumpu

Abstract

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 membrane...Continue Reading

References

Mar 24, 1999·The Journal of Cell Biology·M S LadinskyL A Staehelin
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·C McCormickF Tufaro
Mar 30, 2001·The Journal of Biological Chemistry·A K DattaJ C Paulson
Jun 5, 2002·Annual Review of Biochemistry·Jeffrey D Esko, Scott B Selleck
Jun 28, 2005·Nucleic Acids Research·Dina Schneidman-DuhovnyHaim J Wolfson
Jun 28, 2005·Proteins·Dina Schneidman-DuhovnyHaim J Wolfson
Apr 10, 2010·The Journal of Biological Chemistry·Antti HassinenSakari Kellokumpu
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Sep 4, 2013·Acta Crystallographica. Section D, Biological Crystallography·Bernd KuhnMarkus G Rudolph
Sep 27, 2014·Experimental Cell Research·Jeerawat SoonthornsitNobuhiro Nakamura
Aug 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Benjamin D EngelWolfgang Baumeister
Sep 28, 2015·Journal of Molecular Biology·G C P van ZundertA M J J Bonvin
Oct 18, 2015·Cellular and Molecular Life Sciences : CMLS·Sakari KellokumpuTuomo Glumoff
Jan 13, 2017·Nature Protocols·Dima KozakovSandor Vajda
Sep 22, 2017·Cellular and Molecular Life Sciences : CMLS·Deborah HarrusTuomo Glumoff
Oct 24, 2018·PloS One·Deborah HarrusTuomo Glumoff
Dec 21, 2018·International Journal of Molecular Sciences·Sou Hyun KimYoung-Suk Jung

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Citations

Jan 19, 2021·The Journal of Biological Chemistry·Katarzyna Szymczak-KulusMarcin Czerwinski
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Mar 9, 2021·Frontiers in Plant Science·Olga A ZabotinaRichard Weerts
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Xiaoyan Zhang

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