MCC950 closes the active conformation of NLRP3 to an inactive state

被引：340

作者：

Tapia-Abelian, Ana ^{[1
]}

Angosto-Bazarra, Diego ^{[1
]}

Martinez-Banaclocha, Helios ^{[1
]}

de Torre-Minguela, Carlos ^{[1
]}

Ceron-Carrasco, Jose P. ^{[2
]}

Perez-Sanchez, Horacio ^{[2
]}

Arostegui, Juan, I ^{[3
]}

Pelegrin, Pablo ^{[1
]}

机构：

[1] Univ Clin Hosp Virgen de la Arrixaca, Biomed Res Inst Murcia IMIB Arrixaca, Murcia, Spain

[2] Univ Catolica Murcia UCAM, Comp Engn Dept, Bioinformat & High Performance Comp Res Grp BIO H, Murcia, Spain

[3] Hosp Clin IDIBAPS, Dept Immunol, Barcelona, Spain

来源：

NATURE CHEMICAL BIOLOGY | 2019年 / 15卷 / 06期

基金：

欧洲研究理事会;

关键词：

INFLAMMASOME; ACTIVATION; INHIBITOR; IDENTIFICATION; CASPASE-1; IL-1-BETA; NEK7;

D O I：

10.1038/s41589-019-0278-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：560 / +

页数：14

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