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- Title
Crystal structure of the complex of CLEC12A and an antibody that interferes with binding of diverse ligands.
- Authors
Mori, Shotaro; Nagae, Masamichi; Yamasaki, Sho
- Abstract
C-type lectin receptors (CLRs) are a family of pattern recognition receptors, which detect a broad spectrum of ligands via small carbohydrate-recognition domains (CRDs). CLEC12A is an inhibitory CLR that recognizes crystalline structures such as monosodium urate crystals. CLEC12A also recognizes mycolic acid, a major component of mycobacterial cell walls, and suppresses host immune responses. Although CLEC12A could be a therapeutic target for mycobacterial infection, structural information on CLEC12A was not available. We report here the crystal structures of human CLEC12A (hCLEC12A) in ligand-free form and in complex with 50C1, its inhibitory antibody. 50C1 recognizes human-specific residues on the top face of hCLEC12A CRD. A comprehensive alanine scan demonstrated that the ligand-binding sites of mycolic acid and monosodium urate crystals may overlap with each other, suggesting that CLEC12A utilizes a common interface to recognize different types of ligands. Our results provide atomic insights into the blocking and ligand-recognition mechanisms of CLEC12A and leads to the design of CLR-specific inhibitors.
- Subjects
URATES; CRYSTAL structure; PATTERN perception receptors; MYCOLIC acids; LIGANDS (Chemistry); MYCOBACTERIAL diseases
- Publication
International Immunology, 2024, Vol 36, Issue 6, p279
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxae006