Recognition of microbial glycans by human intelectin-1

  • Nat Struct Mol Biol. 2015 Aug;22(8):603-10. doi: 10.1038/nsmb.3053.
Darryl A Wesener  1 ,  Kittikhun Wangkanont  2 ,  Ryan McBride  3 ,  Xuezheng Song  4 ,  Matthew B Kraft  2 ,  Heather L Hodges  2 ,  Lucas C Zarling  1 ,  Rebecca A Splain  2 ,  David F Smith  4 ,  Richard D Cummings  4 ,  James C Paulson  3 ,  Katrina T Forest  5 ,  Laura L Kiessling  6
Affiliations
  • 1. Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • 2. Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • 3. 1] Department of Cell and Molecular Biology, Scripps Research Institute, La Jolla, California, USA. [2] Department of Chemical Physiology, Scripps Research Institute, La Jolla, California, USA.
  • 4. 1] Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA. [2] Glycomics Center, Emory University School of Medicine, Atlanta, Georgia, USA.
  • 5. Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • 6. 1] Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA. [2] Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
PMID: 26148048 DOI: 10.1038/nsmb.3053
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 does interact with multiple glycan epitopes found exclusively on microbes: β-linked D-galactofuranose (β-Galf), 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-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, 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.