Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal.

对尿酸单钠晶体的 C 型凝集素受体 CLEC12A 介导的免疫识别的机制见解。

• 发表时间: 2024 Mar 16
• 来源期刊: J Biol Chem
• DOI: 10.1016/j.jbc.2024.105765
• PMID: 38367667
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Tang H,Xiao Y,Qian L,Wang Z,Lu M,Yao N,Zhou T,Tian F,Cao L,Zheng P,Dong X

关键词: C-type lectin receptor; CLEC12A; crystal structure; damage-associated molecular pattern; monosodium urate crystal; oligomerization; phagocytic vesicle; single-molecule force spectroscopy

Mesh: Humans; Gout / metabolism; Lectins, C-Type / chemistry immunology; Receptors, Mitogen / chemistry immunology; Uric Acid / chemistry immunology; Protein Domains; Crystallography, X-Ray; Single Molecule Imaging; Cell Line

Abstract

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique \"basic patch\" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.

摘要

CLEC12A,参与免疫稳态的C型凝集素受体家族成员，识别从垂死细胞释放的MSU晶体。然而,CLEC12A介导的MSU晶体识别的分子机制仍不清楚.在这里，我们报道了人CLEC12A-CTLD的晶体结构,并在CLEC12A-CTLD上鉴定了一个独特的"基本补丁"位点,该位点是MSU晶体结合所必需的.同时,我们使用单分子力谱测定了CLEC12A-CTLD和MSU晶体之间的相互作用强度。此外，我们发现CLEC12A聚集在细胞膜上，似乎是MSU晶体的内在化受体。总之,这些发现为理解CLEC12A和MSU晶体之间相互作用的分子机制提供了机制见解。