Recognition of microbial glycans by human intelectin-1

Extensive glycan microarray and structural analyses reveal that human intelectin-1 interacts selectively with microbial glycan epitopes through recognition of a terminal 1,2-diol group, an interaction that would be blocked in human glycans such as α-Neu5Ac. 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 does interact with multiple glycan epitopes found exclusively on microbes: β-linked D -galactofuranose (β-Gal f ), D -phosphoglycerol–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 complexed with 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, has an exocyclic 1,2-diol but does not bind hIntL-1, probably owing to unfavorable steric and electronic effects. hIntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. This ligand selectivity suggests that hIntL-1 functions in microbial surveillance.