Recognition of Bisecting N-Acetylglucosamine

• Published in: The Journal of biological chemistry Vol. 288; no. 47; pp. 33598 - 33610
• Main Authors: Nagae, Masamichi, Yamanaka, Kousuke, Hanashima, Shinya, Ikeda, Akemi, Morita-Matsumoto, Kana, Satoh, Tadashi, Matsumoto, Naoki, Yamamoto, Kazuo, Yamaguchi, Yoshiki
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2013
• Subjects: Bisecting N-Acetylglucosamine; C-type Lectin; Carbohydrate; Crystal Structure; DCIR2; Dendritic Cells; Glycan; Lectin; Receptors; Crystal Structure; Lectin; Receptors; C-type Lectin; Dendritic Cells; Bisecting N-Acetylglucosamine; DCIR2; Carbohydrate; Glycan
• 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. Background: Mouse dendritic cell inhibitory receptor 2 (DCIR2) specifically binds to bisecting GlcNAc-containing N-glycans. Results: The crystal structure of DCIR2 carbohydrate recognition domain in complex with bisected glycan was elucidated. Conclusion: The lectin asymmetrically interacts with the α1-3 arm (GlcNAcβ1–2Man) of the biantennary oligosaccharide including bisecting GlcNAc. Significance: Mouse DCIR2 is the first bisecting GlcNAc-specific lectin to be structurally characterized.