4n32
Structure of langerin CRD with alpha-Me-GlcNAc.
Structural highlights
DiseaseCLC4K_HUMAN Defects in CD207 are the cause of Birbeck granule deficiency (BIRGD) [MIM:613393. It is a condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.[1] [2] FunctionCLC4K_HUMAN Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.[3] [4] [5] [6] Publication Abstract from PubMedLangerin, 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 non-optimal binding of galactose at the primary Ca2+ site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys313, 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 Ile313 packing against the N-acetyl group. The Lys313Ile polymorphism is tightly linked to another SNP that results in the change Asn288Asp, which reduces affinity for glycan ligands by destabilizing the Ca2+ binding site. Langerin with Asp288 and Ile313 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 Asn288Asp and Lys313Ile polymorphisms may affect susceptibility to infection by micro-organisms. Common polymorphisms in human langerin change specificity for glycan ligands.,Feinberg H, Rowntree TJ, Tan SL, Drickamer K, Weis WI, Taylor ME J Biol Chem. 2013 Nov 11. PMID:24217250[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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