Unique Binding Specificities of Proteins toward Isomeric Asparagine-Linked Glycans

• Type of Material: Article
• Authors: Chao Gao, Harvard Medical School; Melinda S. Hanes, Harvard Medical School; Lauren Byrd-Leotis, Emory University; Mohui Wei, Harvard Medical School; Nan Jia, Harvard Medical School; Robert J. Kardish, Harvard Medical School; Tanya McKitrick, Harvard Medical School; David Steinhauer, Emory University; Richard Cummings, Emory University
• Language: English
• Date: 2019-04-18
• Publisher: CELL PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chembiol.2019.01.002
• Title of Journal or Parent Work: CELL CHEMICAL BIOLOGY
• Volume: 26
• Issue: 4
• Start Page: 535
• End Page: +
• Grant/Funding Information: This work was supported by CEIRS grant contract HHSN272201400 to DS and RDC and NIH Grant P41GM103694 to RDC.; NIH grants P41GM103390 and P01GM107012.
• Keywords: N-GLYCANS; OLIGOSACCHARIDES; CHEMOENZYMATIC SYNTHESIS; CELL-LINES; SUBSTRATE-SPECIFICITY; SCALE PRODUCTION; STRUCTURAL DETERMINANTS; HIGH-AFFINITY; Biochemistry & Molecular Biology; COLUMN CHROMATOGRAPHY; Science & Technology; Life Sciences & Biomedicine; LECTIN

Abstract

The glycan ligands recognized by Siglecs, influenza viruses, and galectins, as well as many plant lectins, are not well defined. To explore their binding to asparagine (Asn)-linked N-glycans, we synthesized a library of isomeric multiantennary N-glycans that vary in terminal non-reducing sialic acid, galactose, and N-acetylglucosamine residues, as well as core fucose. We identified specific recognition of N-glycans by several plant lectins, human galectins, influenza viruses, and Siglecs, and explored the influence of sialic acid linkages and branching of the N-glycans. These results show the unique recognition of complex-type N-glycans by a wide variety of glycan-binding proteins and their abilities to distinguish isomeric structures, which provides new insights into the biological roles of these proteins and the uses of lectins in biological applications to identify glycans. Gao et al. chemoenzymatically synthesized a library of naturally occurring asparagine-linked glycan isomers and identified unique glycan-binding specificities of plant lectins, human galectins, influenza viruses, and Siglecs. These results provide important guidance on the biological and clinical applications of these proteins in distinguishing isomeric glycans with certain structural features.