8W9J

Crystal structure of human CLEC12A ectodomain complexed with 50C1 Fab

8W9J の概要

• エントリーDOI: 10.2210/pdb8w9j/pdb
• 分子名称: Anti-human CLEC12A antibody 50C1 light chain, Anti-human CLEC12A antibody 50C1 heavy chain, C-type lectin domain family 12 member A (3 entities in total)
• 機能のキーワード: c-type lectin receptor, inhibitory antibody, clec12a, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 143004.07

構造登録者

Mori, S.,Nagae, M.,Yamasaki, S. (登録日: 2023-09-05, 公開日: 2024-03-06, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.5 Å)