Beilstein Talk on chemical precision tools to dissect protein glycosylation

Beilstein Talks

The Beilstein Talks are an established addition to the projects of the Beilstein-Institut supporting communication and information in science. These online talks are free to attend; a simple registration is all that is required.

Chemical precision tools to dissect protein glycosylation

Ben Schumann / Imperial College London
May 8, 2024, 3–4 pm CEST

Online live talk

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Introduction

The composition of glycoproteins is an undisputed corollary of their function. Understanding the glycoproteome in health and disease is paramount but hampered by the complexity of glycan modifications: hundreds of biosynthetic enzymes in the secretory pathway manifest the cell surface glyco-code. Interdependencies of these enzymes can impact the applicability of classical methods in molecular and cell biology, for instance through compensation or competition events.

Here, I describe our work that complements approaches in molecular cell biology by generating chemical “precision tools” to understand the activities of individual glycosyltransferase enzymes. A key technology is the bump-and-hole tactic in which glycosyltransferases are engineered to accept a chemically modified, bulky nucleotide-sugar substrate. The tactic is applicable to living cells, allowing to trace protein glycosylation introduced in the secretory pathway by bioorthogonal chemistry. We have produced precision tools for a variety of glycosyltransferases, glycan subtypes, and cell types to shed light on the complexity of the secretory pathway.