A novel mechanism for binding of galactose-terminated
glycans by the C-type carbohydrate recognition domain in
blood dendritic cell antigen 2
glycans by the C-type carbohydrate recognition domain in
blood dendritic cell antigen 2
File(s)
Published version
Author(s)
Type
Journal Article
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 Ca2+ 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.
Date Issued
2015-05-20
Date Acceptance
2015-05-14
Citation
Journal of Biological Chemistry, 2015, 290 (27), pp.16759-16771
ISSN
1083-351X
Publisher
American Society for Biochemistry and Molecular Biology
Start Page
16759
End Page
16771
Journal / Book Title
Journal of Biological Chemistry
Volume
290
Issue
27
Copyright Statement
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author’s Choice—Final version free via Creative Commons CC-BY license.
License URL
Sponsor
Wellcome Trust
Identifier
https://www.sciencedirect.com/science/article/pii/S0021925820402339?via%3Dihub
Grant Number
093599/Z/10/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
STRUCTURAL-BASIS
LIGAND-BINDING
LECTIN
RECEPTORS
BDCA-2
EXPRESSION
PROTEIN
CD303
CLEC4C
carbohydrate-binding protein
crystal structure
glycobiology
glycoprotein
lectin
Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Carbohydrate Sequence
Crystallography, X-Ray
Galactose
Humans
Lectins, C-Type
Membrane Glycoproteins
Molecular Sequence Data
Polysaccharides
Receptors, Immunologic
Humans
Galactose
Polysaccharides
Membrane Glycoproteins
Lectins, C-Type
Receptors, Immunologic
Crystallography, X-Ray
Binding Sites
Amino Acid Sequence
Amino Acid Motifs
Carbohydrate Sequence
Molecular Sequence Data
03 Chemical Sciences
06 Biological Sciences
11 Medical and Health Sciences
Biochemistry & Molecular Biology
Publication Status
Published
Date Publish Online
2015-07-03