Terminal Epitope-Dependent Branch Preference of Siglecs Toward N-Glycans

Shuaishuai Wang; Congcong Chen; Minhui Guan; Ding Liu; Xiu-Feng Wan; Lei Li

doi:10.3389/fmolb.2021.645999

Terminal Epitope-Dependent Branch Preference of Siglecs Toward N-Glycans

Front Mol Biosci. 2021 Apr 29:8:645999. doi: 10.3389/fmolb.2021.645999. eCollection 2021.

Authors

Shuaishuai Wang¹, Congcong Chen¹, Minhui Guan^{2

3

4}, Ding Liu¹, Xiu-Feng Wan^{2

3

4

5}, Lei Li¹

Affiliations

¹ Department of Chemistry, Georgia State University, Atlanta, GA, United States.
² MU Center for Influenza and Emerging Infectious Diseases, University of Missouri, Columbia, MO, United States.
³ Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, United States.
⁴ Bond Life Sciences Center, University of Missouri, Columbia, MO, United States.
⁵ Department of Electrical Engineering and Computer Science, College of Engineering, University of Missouri, Columbia, MO, United States.

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 N-glycan binding profiles of a set of Siglecs by using a complex asymmetric N-glycan microarray. Our results showed that Siglecs had unique terminal epitope-dependent branch preference when recognizing asymmetric N-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 N-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.

Keywords: Neu5Ac; Neu5Gc; Siglecs; asymmetric N-glycan; microarray.