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DOI	10.1073/pnas.2026102118
	Probing the binding specificities of human Siglecs by cell-based glycan arrays
	Büll C.; Nason R.; Sun L.; Van Coillie J.; Sørensen D.M.; Moons S.J.; Yang Z.; Arbitman S.; Fernandes S.M.; Furukawa S.; McBride R.; Nycholat C.M.; Adema G.J.; Paulson J.C.; Schnaar R.L.; Boltje T.J.; Clausen H.; Narimatsu Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Siglecs are a family of sialic acid–binding receptors expressed by cells of the immune system and a few other cell types capable of modulating immune cell functions upon recognition of sialoglycan ligands. While human Siglecs primarily bind to sialic acid residues on diverse types of glycoproteins and glycolipids that constitute the sialome, their fine binding specificities for elaborated complex glycan structures and the contribution of the glycoconjugate and protein context for recognition of sialoglycans at the cell surface are not fully elucidated. Here, we generated a library of isogenic human HEK293 cells with combinatorial loss/gain of individual sialyltransferase genes and the introduction of sulfotransferases for display of the human sialome and to dissect Siglec interactions in the natural context of glycoconjugates at the cell surface. We found that Siglec-4/7/15 all have distinct binding preferences for sialylated GalNAc-type O-glycans but exhibit selectivity for patterns of O-glycans as presented on distinct protein sequences. We discovered that the sulfotransferase CHST1 drives sialoglycan binding of Siglec-3/8/7/15 and that sulfation can impact the preferences for binding to O-glycan patterns. In particular, the branched Neu5Acα2–3(6-O-sulfo)Galβ1–4GlcNAc (6′-Su-SLacNAc) epitope was discovered as the binding epitope for Siglec-3 (CD33) implicated in late-onset Alzheimer’s disease. The cell-based display of the human sialome provides a versatile discovery platform that enables dissection of the genetic and biosynthetic basis for the Siglec glycan interactome and other sialic acid–binding proteins. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CD33; Cell-based glycan array; Sialome; Sialyltransferase; Siglecs
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179756
作者单位	Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark; Cluster for Molecular Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, 6525 AJ, Netherlands; Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Molecular Medicine, The Scripps Research Institute, San Diego, CA 92037, United States; Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, 6525 GA, Netherlands; GlycoDisplay ApS, Copenhagen, 2100 N, Denmark
推荐引用方式 GB/T 7714	Büll C.,Nason R.,Sun L.,et al. Probing the binding specificities of human Siglecs by cell-based glycan arrays[J],2021,118(17).
APA	Büll C..,Nason R..,Sun L..,Van Coillie J..,Sørensen D.M..,...&Narimatsu Y..(2021).Probing the binding specificities of human Siglecs by cell-based glycan arrays.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Büll C.,et al."Probing the binding specificities of human Siglecs by cell-based glycan arrays".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).