AIM2炎性小体的激活与调控：结构视角
AIM2 inflammasome activation and regulation: A structural perspective.
作者信息
Wang Bing, Yin Qian
机构信息
Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, United States.
Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, United States.
出版信息
J Struct Biol. 2017 Dec;200(3):279-282. doi: 10.1016/j.jsb.2017.08.001. Epub 2017 Aug 13.
Abstract
Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes. In this review, we track the AIM2 inflammasome activation process step by step, using high-resolution structures to illustrate the overall architecture of AIM2 inflammasome and its assembly and regulatory mechanisms.
摘要
黑色素瘤缺乏因子2（AIM2）炎性小体是一个多蛋白平台，可识别异常的细胞质双链DNA并诱导细胞因子成熟、释放和焦亡。它由AIM2、含半胱天冬酶激活和招募结构域（CARD）的凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1组成。最近的X射线晶体学和高分辨率冷冻电子显微镜（cryo-EM）研究揭示了AIM2炎性小体激活和调控过程中的一系列结构。多个步骤中一个共同的突出特征是高阶结构的组装，特别是由上游分子形成的螺旋丝，而不是化学计量复合物。在这篇综述中，我们逐步追踪AIM2炎性小体的激活过程，利用高分辨率结构来说明AIM2炎性小体的整体结构及其组装和调控机制。
相似文献
1
AIM2 inflammasome activation and regulation: A structural perspective.AIM2炎性小体的激活与调控：结构视角
J Struct Biol. 2017 Dec;200(3):279-282. doi: 10.1016/j.jsb.2017.08.001. Epub 2017 Aug 13.
2
AIM2 Inflammasome Assembly and Signaling.AIM2 炎性小体的组装和信号转导。
Adv Exp Med Biol. 2019;1172:143-155. doi: 10.1007/978-981-13-9367-9_7.
3
The hierarchical structural architecture of inflammasomes, supramolecular inflammatory machines.炎性小体的分层结构架构，超分子炎症机器。
Curr Opin Struct Biol. 2015 Apr;31:75-83. doi: 10.1016/j.sbi.2015.03.014. Epub 2015 Apr 13.
4
Immunobiology and structural biology of AIM2 inflammasome.AIM2 炎症小体的免疫生物学和结构生物学。
Mol Aspects Med. 2020 Dec;76:100869. doi: 10.1016/j.mam.2020.100869. Epub 2020 Jul 10.
5
Structural mechanisms of inflammasome assembly.炎性小体组装的结构机制。
FEBS J. 2015 Feb;282(3):435-44. doi: 10.1111/febs.13133. Epub 2014 Nov 21.
6
Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.通过AIM2的PYD细丝的冷冻电镜结构揭示的PYD组装中的可塑性。
Cell Discov. 2015;1:15013-. doi: 10.1038/celldisc.2015.13. Epub 2015 Jun 23.
7
Digital signaling network drives the assembly of the AIM2-ASC inflammasome.数字信号网络驱动 AIM2-ASC 炎症小体的组装。
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E1963-E1972. doi: 10.1073/pnas.1712860115. Epub 2018 Feb 12.
8
Knockdown of the AIM2 molecule attenuates ischemia-reperfusion-induced spinal neuronal pyroptosis by inhibiting AIM2 inflammasome activation and subsequent release of cleaved caspase-1 and IL-1β.敲低 AIM2 分子可通过抑制 AIM2 炎性小体的激活及其随后的半胱天冬酶-1 和 IL-1β的释放，减轻缺血再灌注诱导的脊髓神经元细胞焦亡。
Neuropharmacology. 2019 Dec 1;160:107661. doi: 10.1016/j.neuropharm.2019.05.038. Epub 2019 Jun 8.
9
Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC.AIM2 外源双链 DNA 传感器的组装驱动激活为下游 ASC 提供了聚合模板。
Nat Commun. 2015 Jul 22;6:7827. doi: 10.1038/ncomms8827.
10
Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes.ASC 依赖性炎症小体组装的统一聚合机制。
Cell. 2014 Mar 13;156(6):1193-1206. doi: 10.1016/j.cell.2014.02.008.
引用本文的文献
1
The immune-related prognostic gene AIM2 promotes pancreatic cancer progression via inflammasome.免疫相关预后基因AIM2通过炎性小体促进胰腺癌进展。
Sci Rep. 2025 Aug 13;15(1):29733. doi: 10.1038/s41598-025-12651-x.
2
The pyroptosis-related gene signature predicts prognosis and reveals immune microenvironment infiltration in reclassified glioblastoma based on 2021 WHO classification.基于2021年世界卫生组织分类，焦亡相关基因特征预测重新分类的胶质母细胞瘤的预后并揭示免疫微环境浸润。
Front Immunol. 2025 Jul 21;16:1617036. doi: 10.3389/fimmu.2025.1617036. eCollection 2025.
3
Potential diagnostic and therapeutic gene in chronic low back pain through pyroptosis modulation: A silico study based on the dataset analysis.通过焦亡调节治疗慢性腰痛的潜在诊断和治疗基因：基于数据集分析的计算机模拟研究
Sci Rep. 2025 Jul 16;15(1):25767. doi: 10.1038/s41598-025-06756-6.
4
From Bat to Worse: The Pivotal Role of Bats for Viral Zoonosis.从蝙蝠到更糟：蝙蝠在病毒人畜共患病中的关键作用。
Microb Biotechnol. 2025 Jul;18(7):e70190. doi: 10.1111/1751-7915.70190.
5
The emerging role of cuproptosis in spinal cord injury.铜死亡在脊髓损伤中的新作用。
Front Immunol. 2025 Jun 16;16:1595852. doi: 10.3389/fimmu.2025.1595852. eCollection 2025.
6
Identifying Common Diagnostic Biomarkers and Therapeutic Targets between COPD and Sepsis: A Bioinformatics and Machine Learning Approach.识别慢性阻塞性肺疾病（COPD）和脓毒症之间的常见诊断生物标志物和治疗靶点：一种生物信息学和机器学习方法。
Int J Chron Obstruct Pulmon Dis. 2025 May 28;20:1761-1786. doi: 10.2147/COPD.S510846. eCollection 2025.
7
Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels.通过协同高阶组装形成进行信号传导：连接分子和细胞水平的证据
Biochem J. 2025 Mar 5;482(5):275-294. doi: 10.1042/BCJ20220094.
8
Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.炎性小体：造血干细胞移植中的潜在治疗靶点。
Cell Commun Signal. 2024 Dec 18;22(1):596. doi: 10.1186/s12964-024-01974-3.
9
Molecular characteristics, clinical significance and cancer‑immune interactions of pyroptosis‑related genes in colorectal cancer.结直肠癌中焦亡相关基因的分子特征、临床意义及癌症免疫相互作用
Oncol Lett. 2024 Dec 5;29(2):89. doi: 10.3892/ol.2024.14835. eCollection 2025 Feb.
10
Neutrophil extracellular traps facilitate liver inflammation/fibrosis progression by entering macrophages and triggering AIM2 inflammasome-dependent pyroptosis.中性粒细胞胞外诱捕网通过进入巨噬细胞并触发 AIMP 炎性小体依赖性细胞焦亡来促进肝脏炎症/纤维化进展。
Cell Commun Signal. 2024 Nov 20;22(1):556. doi: 10.1186/s12964-024-01944-9.
本文引用的文献
1
NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain.NLRP3炎性小体的组装受吡喃结构域磷酸化的调节。
J Exp Med. 2017 Jun 5;214(6):1725-1736. doi: 10.1084/jem.20160933. Epub 2017 May 2.
2
Inflammasomes: mechanism of assembly, regulation and signalling.炎症小体：组装、调控和信号转导机制。
Nat Rev Immunol. 2016 Jul;16(7):407-20. doi: 10.1038/nri.2016.58. Epub 2016 Jun 13.
3
Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism.半胱天冬酶-1聚合的分子基础及其通过一种新的封端机制受到的抑制作用。
Nat Struct Mol Biol. 2016 May;23(5):416-25. doi: 10.1038/nsmb.3199. Epub 2016 Apr 4.
4
Filament assemblies in foreign nucleic acid sensors.外源核酸传感器中的细丝组装体。
Curr Opin Struct Biol. 2016 Apr;37:134-44. doi: 10.1016/j.sbi.2016.01.011. Epub 2016 Feb 7.
5
The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex.先天性免疫传感器IFI16通过沿双链扫描来识别细胞核中的外源DNA。
Elife. 2015 Dec 16;4:e11721. doi: 10.7554/eLife.11721.
6
AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity.AIM2炎性小体在感染、癌症和自身免疫中的作用：在DNA传感、炎症和固有免疫中的角色
Eur J Immunol. 2016 Feb;46(2):269-80. doi: 10.1002/eji.201545839. Epub 2015 Dec 28.
7
Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.通过AIM2的PYD细丝的冷冻电镜结构揭示的PYD组装中的可塑性。
Cell Discov. 2015;1:15013-. doi: 10.1038/celldisc.2015.13. Epub 2015 Jun 23.
8
Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC.AIM2 外源双链 DNA 传感器的组装驱动激活为下游 ASC 提供了聚合模板。
Nat Commun. 2015 Jul 22;6:7827. doi: 10.1038/ncomms8827.
9
Regulation of inflammasome activation.炎性小体激活的调控
Immunol Rev. 2015 May;265(1):6-21. doi: 10.1111/imr.12296.
10
SMOCs: supramolecular organizing centres that control innate immunity.SMOCs：控制先天免疫的超分子组织中心。
Nat Rev Immunol. 2014 Dec;14(12):821-6. doi: 10.1038/nri3757. Epub 2014 Oct 31.
Zotero 插件