3p5h
Structure of the carbohydrate-recognition domain of human Langerin with Laminaritriose
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 mediates the carbohydrate-dependent uptake of pathogens by Langerhans cells in the first step of antigen presentation to the adaptive immune system. Langerin binds to an unusually diverse number of endogenous and pathogenic cell surface carbohydrates, including mannose-containing Ospecific polysaccharides derived from bacterial lipopolysaccharides identified here by probing a microarray of bacterial polysaccharides. Crystal structures of the carbohydrate-recognition domain from human langerin bound to a series of oligomannose compounds, the blood group B antigen, and a fragment of beta-glucan reveal binding to mannose, fucose, and glucose residues by Ca(2+) coordination of vicinal hydroxyl groups with similar stereochemistry. Oligomannose compounds bind through a single-mannose residue, with no other mannose residues contacting the protein directly. There is no evidence for a second Ca(2+)-independent binding site. Likewise, a beta-glucan fragment, Glcbeta1-3Glcbeta1-3Glc, binds to langerin through the interaction of a single-glucose residue with the Ca(2+) site. The fucose moiety of the blood group B trisaccharide Galalpha1-3(Fucalpha1-2)Gal also binds to the Ca(2+) site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue. Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO(4)-Galbeta1-4GlcNAc also coordinate Ca(2+), a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites. Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site. Structural Basis for Langerin Recognition of Diverse Pathogen and Mammalian Glycans through a Single Binding Site.,Feinberg H, Taylor ME, Razi N, McBride R, Knirel YA, Graham SA, Drickamer K, Weis WI J Mol Biol. 2010 Nov 26. PMID:21112338[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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