Mass spectrometry-based shotgun glycomics for discovery of natural ligands of glycan-binding proteins. (December 2022)

• Record Type: Journal Article
• Authors: Bui, Duong T.; Kitova, Elena N.; Mahal, Lara K.; Klassen, John S.
• Is Part Of: Current opinion in structural biology. Volume 77(2022)
• Publication Date: 2022-12
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2022.102448
• Languages: English
• ISSNs: 0959-440X

Abstract

Abstract: The non-covalent associations of complex carbohydrates (glycans) with glycan-binding proteins mediate many important physiological and pathophysiological processes. Identifying these interactions is essential to understanding their diverse biological functions and enables the development of new disease treatments and diagnostics. Knowledge of the repertoire of glycans recognized by most glycan-binding proteins and their affinities is incomplete. Mass spectrometry-based screening of natural glycan libraries has emerged as a promising approach to defining the glycan interactome of glycan-binding proteins. Here, we review recent advances in mass spectrometry-based natural library screening that have led to the discovery of glycan ligands of endogenous and exogenous proteins and illuminated their binding specificities. Graphical abstract: Image 1 Highlights: Mass spectrometry-based shotgun glycomics (MS-SG), performed with the catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay, is a powerful approach to discover the ligands of glycan-binding proteins. CaR-ESI-MS allows for the simultaneous detection of glycan ligands, with a range of affinities, in mixtures. Affinities can be ranked by combining the relative abundances of released glycan ligands (measured by CaR-ESI-MS) with the relative concentrations of fluorophore-labeled glycans (measured by hydrophilic interaction liquid chromatography).