Novel lamprey antibody recognizes terminal sulfated galactose epitopes on mammalian glycoproteins

• Type of Material: Article
• Authors: Tanya R McKitrick, Harvard Medical School; Steffen M Bernard, The Scripps Research Institute, La Jolla; Alexander J Noll, Harvard Medical School; Bernard C Collins, Scripps Research Institute; Christopher K Goth, Harvard Medical School; Alyssa M McQuillan, Harvard Medical School; Jamie Heimburg-Molinaro, Harvard Medical School; Brantley R Herrin, Emory University; Ian A Wilson, The Scripps Research Institute, La Jolla; Max Cooper, Emory University; Richard Cummings, Emory University
• Language: English
• Date: 2021-06-03
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s42003-021-02199-7
• Title of Journal or Parent Work: COMMUNICATIONS BIOLOGY
• Volume: 4
• Issue: 1
• Start Page: 674
• End Page: 674
• Keywords: Life Sciences & Biomedicine; Science & Technology - Other Topics; IDENTIFICATION; ASPARAGINE-LINKED OLIGOSACCHARIDES; L-SELECTIN; Science & Technology; VARIABLE LYMPHOCYTE RECEPTORS; Life Sciences & Biomedicine - Other Topics; MASS-SPECTROMETRY; Biology; SIALIC ACIDS; HIGH-AFFINITY; CELL-ADHESION MOLECULE; N-GLYCANS; RESPIRATORY MUCINS; Multidisciplinary Sciences
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

The terminal galactose residues of N- and O-glycans in animal glycoproteins are often sialylated and/or fucosylated, but sulfation, such as 3-O-sulfated galactose (3-O-SGal), represents an additional, but poorly understood modification. To this end, we have developed a novel sea lamprey variable lymphocyte receptor (VLR) termed O6 to explore 3-O-SGal expression. O6 was engineered as a recombinant murine IgG chimera and its specificity and affinity to the 3-O-SGal epitope was defined using a variety of approaches, including glycan and glycoprotein microarray analyses, isothermal calorimetry, ligand-bound crystal structure, FACS, and immunohistochemistry of human tissue macroarrays. 3-O-SGal is expressed on N-glycans of many plasma and tissue glycoproteins, but recognition by O6 is often masked by sialic acid and thus exposed by treatment with neuraminidase. O6 recognizes many human tissues, consistent with expression of the cognate sulfotransferases (GAL3ST-2 and GAL3ST-3). The availability of O6 for exploring 3-O-SGal expression could lead to new biomarkers for disease and aid in understanding the functional roles of terminal modifications of glycans and relationships between terminal sulfation, sialylation and fucosylation.