PDBsum entry 4n35

Sugar binding protein

PDB id: 4n35

Contents

Protein chains

128 a.a.

Ligands

BGC-GAL-NAG ×3

GAL-NAG

Metals

_CA ×4

Waters ×591

References listed in PDB file

Key reference

• Title: Common polymorphisms in human langerin change specificity for glycan ligands.
• Authors: H.Feinberg, T.J.Rowntree, S.L.Tan, K.Drickamer, W.I.Weis, M.E.Taylor.
• Ref.: J Biol Chem, 2013, 288, 36762-36771. [DOI no: 10.1074/jbc.M113.528000]
• PubMed id: 24217250

Abstract

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.