Gender:Male
Date of Birth:1977-04-06
Alma Mater:Peking University
Education Level:Postgraduate (Doctoral)
[MORE] Academic Honor:2021 Winner of National Science Fund for Distinguished Young Scholars
北京大学黄廷方／信和青年杰出学者奖
博雅青年学者奖
Impact Factor:49.0
DOI number:10.1038/s41586-022-04671-8
Journal:Nature
Abstract: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.
Discipline:Natural Science
Document Type:J
Volume:605
Page Number:567-574
Translation or Not:no
Date of Publication:2022-04-27
Included Journals:SCI
First Author:Shuwen Zhang,Shitao Zou
Correspondence Author:Youdong Mao
All the Authors:Deyao Yin,Lihong Zhao,Daniel Finley,Zhaolong Wu
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