北京大学官网北京大学新闻网 English
毛有东
点赞:
毛有东
点赞:
论文成果
USP14-regulated allostery of the human proteasome by time-resolved cryo-EM
发布时间:2022-06-24点击次数:
影响因子: 49.0
DOI码: 10.1038/s41586-022-04671-8
发表刊物: Nature
摘要: The NLRP3 inflammasome can be activated by stimuli that include nigericin, uric acid crystals, amyloid-β fibrils and extracellular ATP. The mitotic kinase NEK7 licenses the assembly and activation of the NLRP3 inflammasome in interphase. Here we report a cryo-electron microscopy structure of inactive human NLRP3 in complex with NEK7, at a resolution of 3.8 Å. The earring-shaped NLRP3 consists of curved leucine-rich-repeat and globular NACHT domains, and the C-terminal lobe of NEK7 nestles against both NLRP3 domains. Structural recognition between NLRP3 and NEK7 is confirmed by mutagenesis both in vitro and in cells. Modelling of an active NLRP3-NEK7 conformation based on the NLRC4 inflammasome predicts an additional contact between an NLRP3-bound NEK7 and a neighbouring NLRP3. Mutations to this interface abolish the ability of NEK7 or NLRP3 to rescue NLRP3 activation in NEK7-knockout or NLRP3-knockout cells. These data suggest that NEK7 bridges adjacent NLRP3 subunits with bipartite interactions to mediate the activation of the NLRP3 inflammasome.
学科门类: 理学
文献类型: J
卷号: 605
页面范围: 567-574
是否译文:
发表时间: 2022-04-27
收录刊物: SCI
第一作者: Shuwen Zhang
第一作者: Shitao Zou
通讯作者: Youdong Mao
合写作者: Deyao Yin
合写作者: Lihong Zhao
合写作者: Daniel Finley
合写作者: Zhaolong Wu