NLRP3 炎症小体组装和激活的结构机制

IF 26.9 1区 医学 Q1 IMMUNOLOGY Annual review of immunology Pub Date : 2023-04-26 Epub Date: 2023-02-07 DOI:10.1146/annurev-immunol-081022-021207
Jianing Fu, Hao Wu
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引用次数: 0

摘要

作为先天性免疫系统中的一个重要传感器,NLRP3 能检测到外源性病原体入侵和内源性细胞损伤,并通过形成 NLRP3 炎性体(一种能激活 caspase-1 的超分子复合物)做出反应。NLRP3 炎性体的三个主要组成部分是 NLRP3(捕获危险信号并招募下游分子)、caspase-1(诱导细胞因子 IL-1β 和 IL-18 的成熟,并处理 gasdermin D,以介导细胞因子的释放和脓毒症)和 ASC(凋亡相关斑点样蛋白,含有一个 caspase 招募结构域),后者是连接 NLRP3 和 caspase-1 的桥梁。在这篇文章中,我们回顾了已获得的有关 NLRP3 炎症小体及其成分或亚复合物的结构信息,特别关注非活性 NLRP3 笼、活性 NLRP3-NEK7(NIMA 相关激酶 7)-ASC 炎症小体盘、炎症小体的 PYD-PYD 和 CARD-CARD 同型丝状支架。我们进一步揭示了 NLRP3 炎症小体组装和激活的结构衍生机制。
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Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation.

As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage and responds by forming the NLRP3 inflammasome, a supramolecular complex that activates caspase-1. The three major components of the NLRP3 inflammasome are NLRP3, which captures the danger signals and recruits downstream molecules; caspase-1, which elicits maturation of the cytokines IL-1β and IL-18 and processing of gasdermin D to mediate cytokine release and pyroptosis; and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), which functions as a bridge connecting NLRP3 and caspase-1. In this article, we review the structural information that has been obtained on the NLRP3 inflammasome and its components or subcomplexes, with special focus on the inactive NLRP3 cage, the active NLRP3-NEK7 (NIMA-related kinase 7)-ASC inflammasome disk, and the PYD-PYD and CARD-CARD homotypic filamentous scaffolds of the inflammasome. We further implicate structure-derived mechanisms for the assembly and activation of the NLRP3 inflammasome.

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来源期刊
Annual review of immunology
Annual review of immunology 医学-免疫学
CiteScore
57.20
自引率
0.70%
发文量
29
期刊介绍: The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.
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