Inflammasomes are oligomeric signaling complexes that promote caspase activation and maturation of proinflammatory cytokines. Structural and biophysical studies have shed light on the mechanisms of nucleic acid recognition and signaling complex assembly involving the AIM2 (absent in myeloma 2) and IFI16 (γ-interferon-inducible protein 16) inflammasomes. However, our understanding of the mechanisms of the NLRP3 (nucleotide-binding oligomerization-like receptor family, pyrin domain-containing protein 3) activation, either by nucleic acids or by other reported stimuli, has remained elusive. Exciting recent progress on the filament formation by the ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) pyrin domain and the IFI16-double stranded DNA complex has established that the formation of higher order polymers is one of the general mechanisms for signaling platform assembly in innate immune system. The paradigm-changing discovery of the extracellular function of the NLRP3-ASC inflammasome has opened the door for therapeutic targeting the inflammasome filament formation for various clinical conditions. Future characterization of the canonical and non-canonical inflammasome complexes will undoubtedly reveal more surprises on their structure and function and enrich our understanding of the molecular mechanisms of ligand recognition, activation, and regulation.

中文翻译：

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核酸感应炎症小体。

炎症小体是促进胱天蛋白酶激活和促炎细胞因子成熟的寡聚信号复合物。结构和生物物理研究揭示了涉及AIM2（骨髓瘤2中不存在）和IFI16（γ-干扰素可诱导蛋白16）炎性小体的核酸识别和信号转导复杂装配的机制。然而，我们对通过核酸或其他报道的刺激对NLRP3（核苷酸结合的寡聚样受体家族，含吡喃结构域的蛋白质3）激活的机制的了解仍然不清楚。通过ASC（含有胱天蛋白酶募集结构域的细胞凋亡相关斑点样蛋白）吡啶结构域和IFI16-双链DNA复合物在长丝形成方面的最新进展令人振奋，已确定高级聚合物的形成是形成这种结构的一般机制之一。先天免疫系统中的信号平台组装。NLRP3-ASC炎性小体的细胞外功能的范式变化发现为针对各种临床条件的靶向炎性小体细丝形成的治疗方法打开了大门。规范的和非规范的炎症小体复合物的未来表征无疑将揭示其结构和功能方面的更多惊喜，并丰富我们对配体识别，激活和调节的分子机制的理解。