Crystal structure of the complex of CLEC12A and an antibody that interferes with binding of diverse ligands.

IF 4.8 4区 医学 Q2 IMMUNOLOGY International immunology Pub Date : 2024-04-27 DOI:10.1093/intimm/dxae006
Shotaro Mori, Masamichi Nagae, Sho Yamasaki
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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.

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CLEC12A 与干扰多种配体结合的抗体的复合物晶体结构。
C 型凝集素受体(CLR)是一种模式识别受体,通过小型碳水化合物识别结构域(CRD)检测多种配体。CLEC12A 是一种抑制性 CLR,可识别单钠尿酸盐结晶等结晶结构。CLEC12A 还能识别霉菌细胞壁的主要成分霉菌酸,并抑制宿主的免疫反应。虽然 CLEC12A 可能是霉菌感染的治疗靶点,但目前还没有关于 CLEC12A 的结构信息。我们在此报告了人类 CLEC12A 不含配体的晶体结构以及与其抑制性抗体 50C1 复合物的晶体结构。50C1 可识别 hCLEC12A CRD 顶面的人类特异残基。一项全面的丙氨酸扫描显示,霉菌酸和尿酸单钠盐晶体的配体结合位点可能相互重叠,这表明 CLEC12A 利用一个共同的界面来识别不同类型的配体。我们的研究结果从原子角度揭示了 CLEC12A 的阻断和配体识别机制,有助于设计 CLR 特异性抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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