MCC950 closes the active conformation of NLRP3 to an inactive state
MCC950 closes the active conformation of NLRP3 to an inactive state
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DOI：
10.1038/s41589-019-0278-6
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发表时间：
2019-06-01
影响因子：
14.8
通讯作者：
Pelegrin, Pablo
中科院分区：
文献类型：
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作者：
Tapia-Abelian, Ana;Angosto-Bazarra, Diego;Pelegrin, Pablo
NLRP3（含 NOD 样受体热蛋白结构域的蛋白 3）是一种先天免疫传感器，有助于不同疾病的发展，包括单基因自身炎症综合征、痛风、动脉粥样硬化和阿尔茨海默病。磺酰脲类 MCC950 分子是一种 NLRP3 炎性体抑制剂，具有潜在的临床用途。然而，MCC950 的作用机制仍不清楚。在这里，我们描述了 MCC950 在野生型和自身炎症相关 NLRP3 突变体中的作用机制，并证明 MCC950 关闭了活性 NLRP3 的“开放”构象。
NLRP3 (NOD-like receptor pyrin domain-containing protein 3) is an innate immune sensor that contributes to the development of different diseases, including monogenic autoinflammatory syndromes, gout, atherosclerosis, and Alzheimer's disease. The molecule sulfonylurea MCC950 is a NLRP3 inflammasome inhibitor with potential clinical utility. However, the mechanism of action of MCC950 remains unknown. Here, we characterize the mechanism of action of MCC950 in both wild-type and autoinflammatory-related NLRP3 mutants, and demonstrate that MCC950 closes the 'open' conformation of active NLRP3.