Recognition of bisecting N-acetylglucosamine: structural basis for asymmetric interaction with the mouse lectin dendritic cell inhibitory receptor 2

• Published in: The Journal of biological chemistry 2013-11, Vol.288 (47), p.33598-33610
• Main Authors: Nagae, Masamichi, Yamanaka, Kousuke, Hanashima, Shinya, Ikeda, Akemi, Morita-Matsumoto, Kana, Satoh, Tadashi, Matsumoto, Naoki, Yamamoto, Kazuo, Yamaguchi, Yoshiki
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - chemistry; Acetylglucosamine - genetics; Acetylglucosamine - metabolism; Animals; Crystallography, X-Ray; Glycobiology and Extracellular Matrices; Lectins, C-Type - chemistry; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Mice; Protein Binding; Protein Structure, Tertiary; Structure-Activity Relationship
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.513572

Dendritic cell inhibitory receptor 2 (DCIR2) is a C-type lectin expressed on classical dendritic cells. We recently identified the unique ligand specificity of mouse DCIR2 (mDCIR2) toward biantennary complex-type glycans containing bisecting N-acetylglucosamine (GlcNAc). Here, we report the crystal structures of the mDCIR2 carbohydrate recognition domain in unliganded form as well as in complex with an agalactosylated complex-type N-glycan unit carrying a bisecting GlcNAc residue. Bisecting GlcNAc and the α1-3 branch of the biantennary oligosaccharide asymmetrically interact with canonical and non-canonical mDCIR2 residues. Ligand-protein interactions occur directly through mDCIR2-characteristic amino acid residues as well as via a calcium ion and water molecule. Our structural and biochemical data elucidate for the first time the unique binding mode of mDCIR2 for bisecting GlcNAc-containing glycans, a mode that contrasts sharply with that of other immune C-type lectin receptors such as DC-SIGN.