» Articles » PMID: 33996901

Terminal Epitope-Dependent Branch Preference of Siglecs Toward -Glycans

Overview
Specialty Biology
Date 2021 May 17
PMID 33996901
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

Siglecs are sialic acid-binding immunoglobulin-like lectins that play vital roles in immune cell signaling. Siglecs help the immune system distinguish between self and nonself through the recognition of glycan ligands. While the primary binding specificities of Siglecs are known to be divergent, their specificities for complex glycans remain unclear. Herein, we determined -glycan binding profiles of a set of Siglecs by using a complex asymmetric -glycan microarray. Our results showed that Siglecs had unique terminal epitope-dependent branch preference when recognizing asymmetric -glycans. Specifically, human Siglec-3, -9, and -10 prefer the α1-3 branch when Siaα2-6Galβ1-4GlcNAc terminal epitope serves as the binding ligand but prefer the opposite α1-6 branch when Siaα2-3Galβ1-4GlcNAc epitope serves as the ligand. Interestingly, Siglec-10 exhibited dramatic binding divergence toward a pair of Neu5Ac-containing asymmetric -glycan isomers, as well as their Neu5Gc-containing counterparts. This new information on complex glycan recognition by Siglecs provides insights into their biological roles and applications.

Citing Articles

The glycosyltransferase ST3GAL4 drives immune evasion in acute myeloid leukemia by synthesizing ligands for the glyco-immune checkpoint receptor Siglec-9.

Krishnamoorthy V, Daly J, Kim J, Piatnitca L, Yuen K, Kumar B Leukemia. 2024; 39(2):346-359.

PMID: 39551873 PMC: 11794148. DOI: 10.1038/s41375-024-02454-w.


Discovery, classification, evolution and diversity of Siglecs.

Angata T, Varki A Mol Aspects Med. 2022; 90:101117.

PMID: 35989204 PMC: 9905256. DOI: 10.1016/j.mam.2022.101117.


Systematic synthesis of bisected -glycans and unique recognitions by glycan-binding proteins.

Cao X, Wang S, Gadi M, Liu D, Wang P, Wan X Chem Sci. 2022; 13(25):7644-7656.

PMID: 35872821 PMC: 9241959. DOI: 10.1039/d1sc05435j.


CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platforms.

Klamer Z, Harris C, Beirne J, Kelly J, Zhang J, Haab B Glycobiology. 2022; 32(8):679-690.

PMID: 35352123 PMC: 9280547. DOI: 10.1093/glycob/cwac022.

References
1.
Macauley M, Crocker P, Paulson J . Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014; 14(10):653-66. PMC: 4191907. DOI: 10.1038/nri3737. View

2.
Blixt O, Collins B, van den Nieuwenhof I, Crocker P, Paulson J . Sialoside specificity of the siglec family assessed using novel multivalent probes: identification of potent inhibitors of myelin-associated glycoprotein. J Biol Chem. 2003; 278(33):31007-19. DOI: 10.1074/jbc.M304331200. View

3.
Sugiarto G, Lau K, Qu J, Li Y, Lim S, Mu S . A sialyltransferase mutant with decreased donor hydrolysis and reduced sialidase activities for directly sialylating LewisX. ACS Chem Biol. 2012; 7(7):1232-40. PMC: 3521065. DOI: 10.1021/cb300125k. View

4.
Tateno H, Crocker P, Paulson J . Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6'-sulfo-sialyl Lewis X as a preferred glycan ligand. Glycobiology. 2005; 15(11):1125-35. DOI: 10.1093/glycob/cwi097. View

5.
Angata T, Nycholat C, Macauley M . Therapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches. Trends Pharmacol Sci. 2015; 36(10):645-660. PMC: 4593978. DOI: 10.1016/j.tips.2015.06.008. View