Common polymorphisms in human langerin change specificity for glycan ligands

J Biol Chem. 2013 Dec 27;288(52):36762-71. doi: 10.1074/jbc.M113.528000. Epub 2013 Nov 11.


Langerin, a C-type lectin on Langerhans cells, mediates carbohydrate-dependent uptake of pathogens in the first step of antigen presentation to the adaptive immune system. Langerin binds a diverse range of carbohydrates including high mannose structures, fucosylated blood group antigens, and glycans with terminal 6-sulfated galactose. Mutagenesis and quantitative binding assays indicate that salt bridges between the sulfate group and two lysine residues compensate for the nonoptimal binding of galactose at the primary Ca(2+) site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys-313, to isoleucine. Glycan array screening reveals that this amino acid change abolishes binding to oligosaccharides with terminal 6SO4-Gal and enhances binding to oligosaccharides with terminal GlcNAc residues. Structural analysis shows that enhanced binding to GlcNAc may result from Ile-313 packing against the N-acetyl group. The K313I polymorphism is tightly linked to another SNP that results in the change N288D, which reduces affinity for glycan ligands by destabilizing the Ca(2+)-binding site. Langerin with Asp-288 and Ile-313 shows no binding to 6SO4-Gal-terminated glycans and increased binding to GlcNAc-terminated structures, but overall decreased binding to glycans. Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms.

Keywords: CD207; Carbohydrate-binding Protein; Crystal Structure; Genetic Polymorphism; Glycobiology; Lectin; Sulfated Glycans.

Publication types

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

MeSH terms

  • Amino Acid Substitution*
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Binding Sites
  • Calcium / chemistry*
  • Calcium / immunology
  • Calcium / metabolism
  • Crystallography, X-Ray
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infections / genetics
  • Infections / immunology
  • Infections / metabolism
  • Lectins, C-Type / chemistry*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Ligands
  • Mannose-Binding Lectins / chemistry*
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / immunology
  • Mannose-Binding Lectins / metabolism
  • Oligosaccharides / chemistry*
  • Oligosaccharides / genetics
  • Oligosaccharides / immunology
  • Oligosaccharides / metabolism
  • Polymorphism, Single Nucleotide*
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Protein Structure, Tertiary


  • Antigens, CD
  • CD207 protein, human
  • Lectins, C-Type
  • Ligands
  • Mannose-Binding Lectins
  • Oligosaccharides
  • Calcium

Associated data

  • PDB/4N32
  • PDB/4N33
  • PDB/4N34
  • PDB/4N35
  • PDB/4N36
  • PDB/4N37
  • PDB/4N38