4ZET

Blood dendritic cell antigen 2 (BDCA-2) complexed with GalGlcNAcMan

Summary for 4ZET

• Entry DOI: 10.2210/pdb4zet/pdb
• Related: 4ZES
• Descriptor: C-type lectin domain family 4 member C, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose, CALCIUM ION (3 entities in total)
• Functional Keywords: c-type lectin, carbohydrate-binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 35483.68

Authors

Jegouzo, S.A.F.,Feinberg, H.,Dungarwalla, T.,Drickamer, K.,Weis, W.I.,Taylor, M.E. (deposition date: 2015-04-20, release date: 2015-05-27, Last modification date: 2024-11-20)

Primary citation

Jegouzo, S.A.,Feinberg, H.,Dungarwalla, T.,Drickamer, K.,Weis, W.I.,Taylor, M.E.
A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2.
J.Biol.Chem., 290:16759-16771, 2015

PubMed 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.

PubMed: 25995448
DOI: 10.1074/jbc.M115.660613

Experimental method

X-RAY DIFFRACTION (2.9 Å)