Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306, USA.
Adv Exp Med Biol. 2019;1172:143-155. doi: 10.1007/978-981-13-9367-9_7.
AIM2 (absent in melanoma 2) is a cytoplasmic sensor of double-stranded DNA from pathogens or damaged cellular organelles. It recruits ASC (apoptosis-associated specklike protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses via cytokine maturation and pyroptotic cell death. Structural studies from X-ray crystallography, NMR, and cryo-EM have revealed many details in AIM2 inflammasome activation, assembly, and regulation. Many principles learned from AIM2 inflammasome also apply to other inflammasomes. In this chapter, we discuss the interactions between dsDNA and AIM2-like receptors, between AIM2 and adaptor protein ASC, and between ASC and caspase-1 with the focus on helical filament assembly formed by PYD and CARD domains.
AIM2(黑色素瘤 2 缺失)是一种细胞质传感器,用于检测病原体或受损细胞细胞器的双链 DNA。它募集 ASC(含有 CARD 的凋亡相关斑点样蛋白)和半胱天冬酶-1 形成 AIM2 炎性体,激活半胱天冬酶-1,并通过细胞因子成熟和细胞焦亡诱导炎症反应。来自 X 射线晶体学、NMR 和 cryo-EM 的结构研究揭示了 AIM2 炎性体激活、组装和调节的许多细节。从 AIM2 炎性体中学到的许多原则也适用于其他炎性体。在本章中,我们讨论了 dsDNA 与 AIM2 样受体之间、AIM2 与衔接蛋白 ASC 之间以及 ASC 与半胱天冬酶-1 之间的相互作用,重点是 PYD 和 CARD 结构域形成的螺旋丝组装。