Recognition of microbial glycans by human intelectin-1

Nat Struct Mol Biol. 2015 Aug;22(8):603-10. doi: 10.1038/nsmb.3053. Epub 2015 Jul 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carbohydrate Sequence
  • Crystallography, X-Ray
  • Cytokines / chemistry*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Epitopes / chemistry*
  • Epitopes / metabolism
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Lectins / chemistry*
  • Lectins / genetics
  • Lectins / metabolism
  • Ligands
  • Lipopolysaccharides / chemistry*
  • Lipopolysaccharides / metabolism
  • Mice
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Monosaccharides / chemistry
  • Monosaccharides / metabolism
  • Polysaccharides / chemistry*
  • Polysaccharides / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Streptococcus pneumoniae / chemistry
  • Streptococcus pneumoniae / metabolism
  • Surface Plasmon Resonance

Substances

  • Cytokines
  • Epitopes
  • GPI-Linked Proteins
  • ITLN1 protein, human
  • Lectins
  • Ligands
  • Lipopolysaccharides
  • Monosaccharides
  • Polysaccharides