4N36

Structure of langerin CRD I313 D288 complexed with Me-GlcNAc

Summary for 4N36

• Entry DOI: 10.2210/pdb4n36/pdb
• Related: 4N32 4N33 4N34 4N35 4N37 4N38
• Descriptor: C-type lectin domain family 4 member K, methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: crd carbohydrate complex, carbohydrate-recognition domain, c-type lectin on langerhans cells, carbohydrate/sugar binding, receptor on langerhans cells, sugar binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane ; Single-pass type II membrane protein : Q9UJ71
• Total number of polymer chains: 4
• Total formula weight: 63374.91

Authors

Feinberg, H.,Rowntree, T.J.W.,Tan, S.L.W.,Drickamer, K.,Weis, W.I.,Taylor, M.E. (deposition date: 2013-10-06, release date: 2013-11-20, Last modification date: 2024-11-27)

Primary citation

Feinberg, H.,Rowntree, T.J.,Tan, S.L.,Drickamer, K.,Weis, W.I.,Taylor, M.E.
Common polymorphisms in human langerin change specificity for glycan ligands.
J.Biol.Chem., 288:36762-36771, 2013

PubMed 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.

PubMed: 24217250
DOI: 10.1074/jbc.M113.528000

Experimental method

X-RAY DIFFRACTION (1.85 Å)