دورية أكاديمية
Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains.
| العنوان: | Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains. |
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| المؤلفون: | Khoder-Agha, Fawzi, Harrus, Deborah, Brysbaert, Guillaume, Lensink, Marc, Harduin Lepers, Anne, Glumoff, Tuomo, Kellokumpu, Sakari |
| المساهمون: | Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576 |
| بيانات النشر: | American Society for Biochemistry & Molecular Biology (ASBMB) |
| سنة النشر: | 2021 |
| المجموعة: | LillOA (Lille Open Archive - Université de Lille) |
| مصطلحات موضوعية: | Animals, Antigens, CD, Binding Sites, CHO Cells, COS Cells, Chlorocebus aethiops, Cricetinae, Cricetulus, Fluorescence Resonance Energy Transfer, Galactosyltransferases, Golgi Apparatus, Molecular Docking Simulation, Protein Multimerization, Sialyltransferases, Static Electricity, galactosyltransferase, glycosyltransferase, molecular interplay, protein complex, protein–protein interaction, β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) |
| الوصف: | 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 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 glycan synthesis. ; 294 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | THE JOURNAL OF BIOLOGICAL CHEMISTRY; J. Biol. Chem.; http://hdl.handle.net/20.500.12210/34755.2Test |
| الإتاحة: | https://doi.org/20.500.12210/34755.2Test https://hdl.handle.net/20.500.12210/34755.2Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.92DD9CF5 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |