Immunobiology and Structural Biology of AIM2 Inflammasome
Overview
Molecular Biology
Affiliations
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.
Wang L, Xu X, Su S, Li B, Zhang K, Yu X Sci Rep. 2024; 14(1):31851.
PMID: 39738518 PMC: 11685590. DOI: 10.1038/s41598-024-83027-w.
Zhao J, Cui Y, Zhou H, Zhou D, Che Z, Zhang N Transl Cancer Res. 2024; 13(11):6255-6272.
PMID: 39697705 PMC: 11651761. DOI: 10.21037/tcr-24-1403.
Zhang Y, Wu R, Zhan X, Wang X, Xiang L, Duan Y Cell Commun Signal. 2024; 22(1):556.
PMID: 39568027 PMC: 11577833. DOI: 10.1186/s12964-024-01944-9.
Role of inflammasomes and neuroinflammation in epilepsy.
Hollis A, Lukens J Immunol Rev. 2024; 329(1):e13421.
PMID: 39523682 PMC: 11744240. DOI: 10.1111/imr.13421.
The Role of the AIM2 Gene in Obesity-Related Glucose and Lipid Metabolic Disorders: A Recent Update.
Zhang Y, Xuan X, Ye D, Liu D, Song Y, Gao F Diabetes Metab Syndr Obes. 2024; 17:3903-3916.
PMID: 39465122 PMC: 11512477. DOI: 10.2147/DMSO.S488978.