Novel lamprey antibody recognizes terminal sulfated galactose epitopes on mammalian glycoproteins

Citation:

McKitrick TR, Bernard SM, Noll AJ, Collins BC, Goth CK, McQuillan AM, Heimburg-Molinaro J, Herrin BR, Wilson IA, Cooper MD, et al. Novel lamprey antibody recognizes terminal sulfated galactose epitopes on mammalian glycoproteins. Commun Biol. 2021;4 :674.

Date Published:

Jun 3

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.

Notes:

McKitrick, Tanya RBernard, Steffen MNoll, Alexander JCollins, Bernard CGoth, Christoffer KMcQuillan, Alyssa MHeimburg-Molinaro, JamieHerrin, Brantley RWilson, Ian ACooper, Max DCummings, Richard DengR24GM137763/U.S. Department of Health & Human Services | National Institutes of Health (NIH)R01A1042266/U.S. Department of Health & Human Services | National Institutes of Health (NIH)T32 AI074492/AI/NIAID NIH HHS/P30 GM138396/GM/NIGMS NIH HHS/U01CA199882/U.S. Department of Health & Human Services | National Institutes of Health (NIH)P41GM103694/U.S. Department of Health & Human Services | National Institutes of Health (NIH)T32AI074492/U.S. Department of Health & Human Services | National Institutes of Health (NIH)U01 CA199882/CA/NCI NIH HHS/P41 GM103393/GM/NIGMS NIH HHS/R24 GM137763/GM/NIGMS NIH HHS/R01AI072435/U.S. Department of Health & Human Services | National Institutes of Health (NIH)P41 GM103694/GM/NIGMS NIH HHS/R01 AI072435/AI/NIAID NIH HHS/EnglandCommun Biol. 2021 Jun 3;4(1):674. doi: 10.1038/s42003-021-02199-7.