Recognition of microbial glycans by human intelectin-1

Abstract

The glycans displayed on mammalian cells can differ markedly from those on microbes. Such differences could, in principle, be read by carbohydrate-binding proteins, or lectins. We used glycan microarrays to show that human intelectin-1 (hIntL-1) does not bind known human glycan epitopes but interacts with multiple glycan epitopes found exclusively on microbes: β-linked d-galactofuranose (β-Galf), d-phospho-glycerol-modified glycans, heptoses, d-glycero-d-talo-oct-2-ulosonic acid (KO) and 3-deoxy-d-manno-oct–2-ulosonic acid (KDO). The 1.6 Å resolution crystal structure of hIntL-1 bound to β-Galf revealed that hIntL-1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diols. N-Acetylneuraminic acid (Neu5Ac), a sialic acid widespread in human glycans, possesses an exocyclic 1,2-diol but does not bind hInt-1, likely due to unfavorable steric and electronic effects. Human IntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. This ligand selectivity suggests hIntL-1 functions in microbial surveillance.

Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition

“…Specifically, it has been suggested that hIntL-1 recognizes furanose carbohydrate residues, including galactofuranose (Galf) and ribose (5). Our studies of hIntl-1 indicate that it does not bind ribose, but it does interact with ␤-Galf residues (26) and is thus not a general furanose-binding lectin. Analysis using glycan microarrays revealed that hIntL-1 does not bind any of the tested human glycans but rather binds diverse microbial glycan epitopes.…”

“…None of these epitopes are present on human glycans. In accord with its glycan specificity, hIntL-1 binds microbial cell surfaces, supporting a role for hIntL-1 in the recognition of intact microbes (26). Given these recognition properties and the presence of intelectins in diverse species, an intriguing possibility is that the intelectins serve as microbial detectors.…”

“…C-type lectins typically use calcium ions to coordinate their carbohydrate ligands, but the intelectins are not members of this family (16,25,27). We recently used x-ray crystallography to determine the structures of apo-hIntL-1 and hIntL-1 complexed to a ␤-Galf glycoside (26). Our results indicate that hIntL-1 binds the exocyclic vicinal diol present in ␤-Galf through direct calcium ion coordination.…”

“…Analysis using glycan microarrays revealed that hIntL-1 does not bind any of the tested human glycans but rather binds diverse microbial glycan epitopes. Specifically, hIntL-1 can interact with ␤-Galf, D-glycerol-1-phosphate (GroP), heptoses, D-glycero-D-talo-oct-2-ulosonic acid, and 3-deoxy-D-manno-oct-2-ulosonic acid (26). None of these epitopes are present on human glycans.…”

Circulating Omentin as a Novel Biomarker for Colorectal Cancer Risk: Data from the EPIC–Potsdam Cohort Study

“…selectively binds to pathogenic organisms, suggesting its functions in microbial surveillance (40). Experimental studies have shown that omentin secretion is induced in endothelial cells by IL6 (41), one of the major inflammatory cytokines in response to infection and tissue damage.…”