title: A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2.
abstract: Blood dendritic cell antigen 2 (BDCA-2; also designated CLEC4C or CD303) is uniquely expressed on plasmacytoid dendritic cells. Stimulation of BDCA-2 with antibodies leads to an anti-inflammatory response in these cells, but the natural ligands for the receptor are not known. The C-type carbohydrate recognition domain in the extracellular portion of BDCA-2 contains a signature motif typical of C-type animal lectins that bind mannose, glucose, or GlcNAc, yet it has been reported that BDCA-2 binds selectively to galactose-terminated, biantennary N-linked glycans. A combination of glycan array analysis and binding competition studies with monosaccharides and natural and synthetic oligosaccharides have been used to define the binding epitope for BDCA-2 as the trisaccharide Galβ1-3/4GlcNAcβ1-2Man. X-ray crystallography and mutagenesis studies show that mannose is ligated to the conserved Ca(2+) in the primary binding site that is characteristic of C-type carbohydrate recognition domains, and the GlcNAc and galactose residues make additional interactions in a wide, shallow groove adjacent to the primary binding site. As predicted from these studies, BDCA-2 binds to IgG, which bears galactose-terminated glycans that are not commonly found attached to other serum glycoproteins. Thus, BDCA-2 has the potential to serve as a previously unrecognized immunoglobulin Fc receptor.
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Sabine A F
authors.initials: SA
authors.lastname: Jégouzo
authors.affiliation: From the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305 and.
authors.forename: Hadar
authors.initials: H
authors.lastname: Feinberg
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Tabassum
authors.initials: T
authors.lastname: Dungarwalla
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Kurt
authors.initials: K
authors.lastname: Drickamer
authors.affiliation: From the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305 and.
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom maureen.taylor@imperial.ac.uk.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Taylor
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C443299:CLEC4C protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011971:Receptors, Immunologic; D005690:Galactose
keywords: CD303; CLEC4C; carbohydrate-binding protein; crystal structure; glycobiology; glycoprotein; lectin