Human Sugar-Binding Protein Exclusively Binds Microbial Sugars

The cells of microbes and their mammalian hosts are decorated with glycans that can be read by carbohydrate-binding proteins known as lectins. By using microarrays with synthetic and microbial glycans, Laura L. Kiessling of the University of Wisconsin, Madison, and coworkers show that one such protein, human intelectin-1, exclusively binds microbial glycans instead of mammalian glycans (Nat. Struct. Mol. Biol. 2015, DOI: 10.1038/nsmb.3053). In particular, intelectin-1 binds the sugar β-linked d-galactofuranose (β-Galf) and other microbial glycans. The researchers solved a crystal structure of intelectin-1 bound to β-Galf. The structure reveals that the protein uses a bound calcium ion to form a bridge between the protein and a terminal 1,2-diol group on the glycan. The protein also interacts with other 1,2-diol-containing microbial carbohydrates, including phosphoglycerol and compounds known as KO and KDO. But the protein doesn’t bind to sialic acid, a sugar commonly found in human glycans that also contains a 1,2-diol. Thus, human intelectin-1 is able to distinguish between microbial and human glycans despite structural similarities. Such ligand selectivity points to a role for human intelectin-1 in microbial surveillance, the researchers say.