Wang Bing, Yin Qian
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.
J Struct Biol. 2017 Dec;200(3):279-282. doi: 10.1016/j.jsb.2017.08.001. Epub 2017 Aug 13.
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.
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。
