8W8T

Crystal structure of human CLEC12A CRD

Summary for 8W8T

• Entry DOI: 10.2210/pdb8w8t/pdb
• Descriptor: C-type lectin domain family 12 member A, SULFATE ION (3 entities in total)
• Functional Keywords: pattern recognition receptor, innate immunitiy, c-type lectin receptor, damps, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 29861.75

Authors

Mori, S.,Nagae, M.,Yamasaki, S. (deposition date: 2023-09-04, release date: 2024-03-06, Last modification date: 2024-10-09)

Primary citation

Mori, S.,Nagae, M.,Yamasaki, S.
Crystal structure of the complex of CLEC12A and an antibody that interferes with binding of diverse ligands.
Int.Immunol., 36:279-290, 2024

PubMed 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.

PubMed: 38386511
DOI: 10.1093/intimm/dxae006

Experimental method

X-RAY DIFFRACTION (2.3 Å)