Immunobiology and structural biology of AIM2 inflammasome.

Immunobiology and structural biology of AIM2 inflammasome.
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DOI:
10.1016/j.mam.2020.100869
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发表时间:
2020-12
影响因子:
10.6
通讯作者:
Yin Q
Yin Q
中科院分区:
医学1区
文献类型:
--
作者:
Wang B;Bhattacharya M;Roy S;Tian Y;Yin Q

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黑色素瘤2(AIM 2)中缺少细胞质传感器,其在识别双链DNA后与含有CARD(ASC)和半胱氨酸天冬氨酸蛋白酶原-1的凋亡相关斑点样蛋白组装以形成多蛋白复合物AIM 2炎性体。来自细菌、病毒或宿主细胞来源的双链DNA触发AIM 2炎性体组装和活化,最终导致促炎细胞因子的分泌和细胞凋亡,以消除微生物感染。因此,许多病原体逃避或抑制AIM 2炎性体以建立感染。另一方面,AIM 2的激活受到多种细胞因子的严格控制,以防止自身炎症。广泛的结构研究已经捕获了AIM 2炎性小体组装中多个步骤的分子细节。这些结构共同揭示了一种有核聚合机制,不仅贯穿于AIM 2炎性小体组装的每个步骤,而且也是免疫信号传导中其他炎性小体和复合物组装的基础。在这篇文章中,我们简要回顾了AIM 2作为细胞质DNA传感器的鉴定,总结了AIM 2炎性小体在感染和疾病中的重要性,并讨论了AIM 2组装,激活和调节的分子机制,使用最近的细胞,生化和结构的结果。
Absent in melanoma 2 (AIM2) is a cytoplasmic sensor that upon recognizing double-stranded DNA assembles with apoptosis-associated speck-like protein containing a CARD (ASC) and procaspase-1 to form the multi-protein complex AIM2 inflammasome. Double-stranded DNA from bacterial, viral, or host cellular origins triggers AIM2 inflammasome assembly and activation, ultimately resulting in secretion of proinflammatory cytokines and pyroptotic cell death in order to eliminate microbial infection. Many pathogens therefore evade or suppress AIM2 inflammasome to establish infection. On the other hand, AIM2 activation is tightly controlled by multiple cellular factors to prevent autoinflammation. Extensive structural studies have captured the molecular details of multiple steps in AIM2 inflammasome assembly. The structures collectively revealed a nucleated polymerization mechanism that not only pervades each step of AIM2 inflammasome assembly, but also underlies assembly of other inflammasomes and complexes in immune signaling. In this article, we briefly review the identification of AIM2 as a cytoplasmic DNA sensor, summarize the importance of AIM2 inflammasome in infections and diseases, and discuss the molecular mechanisms of AIM2 assembly, activation, and regulation using recent cellular, biochemical, and structural results.
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