Wang Shuaishuai, Chen Congcong, Guan Minhui, Liu Ding, Wan Xiu-Feng, Li Lei
Department of Chemistry, Georgia State University, Atlanta, GA, United States.
MU Center for Influenza and Emerging Infectious Diseases, University of Missouri, Columbia, MO, United States.
Front Mol Biosci. 2021 Apr 29;8:645999. doi: 10.3389/fmolb.2021.645999. eCollection 2021.
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.
唾液酸结合免疫球蛋白样凝集素（Siglecs）在免疫细胞信号传导中发挥着至关重要的作用。Siglecs通过识别聚糖配体帮助免疫系统区分自身和非自身。虽然已知Siglecs的主要结合特异性存在差异，但其对复杂聚糖的特异性仍不清楚。在此，我们通过使用复杂的不对称聚糖微阵列确定了一组Siglecs的聚糖结合谱。我们的结果表明，Siglecs在识别不对称聚糖时具有独特的末端表位依赖性分支偏好。具体而言，当唾液酸α2-6半乳糖β1-4N-乙酰葡糖胺末端表位作为结合配体时，人Siglec-3、-9和-10偏好α1-3分支，但当唾液酸α2-3半乳糖β1-4N-乙酰葡糖胺表位作为配体时则偏好相反的α1-6分支。有趣的是，Siglec-10对一对含Neu5Ac的不对称聚糖异构体及其含Neu5Gc的对应物表现出显著的结合差异。关于Siglecs对复杂聚糖识别的这一新信息为其生物学作用和应用提供了见解。
