Recognition of Microbial Glycans by Human Intelectin

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-Gal f ), 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-Gal f 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.