4zes
Blood dendritic cell antigen 2 (BDCA-2) complexed with methyl-mannoside
Structural highlights
FunctionCLC4C_HUMAN Involved in antigen-capturing. Target ligand into antigen processing and peptide-loading compartments for presentation to T-cells. May mediate potent inhibition of induction of IFN-alpha/beta expression in plasmacytoid dendritic cells. May act as a signaling receptor that activates protein-tyrosine kinases and mobilizes intracellular calcium. Does not seem to bind mannose.[1] [2] Publication Abstract from PubMedBlood 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 (CRD) 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, bi-antennary 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 trisaccharides Galbeta1-3/4GlcNAcbeta1-2Man. X-ray crystallography and mutagenesis studies show that mannose is ligated to the conserved Ca2+ in the primary binding site that is characteristic of C-type CRDs, 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. A novel mechanism for binding of galactose-terminated glycans by the C-type carbohydrate-recognition domain in blood dendritic cell antigen 2.,Jegouzo SA, Feinberg H, Dungarwalla T, Drickamer K, Weis WI, Taylor ME J Biol Chem. 2015 May 20. pii: jbc.M115.660613. PMID:25995448[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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