School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia.
Front Immunol. 2021 Nov 17;12:784484. doi: 10.3389/fimmu.2021.784484. eCollection 2021.
TIR (Toll/interleukin-1 receptor/resistance protein) domains are cytoplasmic domains widely found in animals and plants, where they are essential components of the innate immune system. A key feature of TIR-domain function in signaling is weak and transient self-association and association with other TIR domains. An additional new role of TIR domains as catalytic enzymes has been established with the recent discovery of NAD-nucleosidase activity by several TIR domains, mostly involved in cell-death pathways. Although self-association of TIR domains is necessary in both cases, the functional specificity of TIR domains is related in part to the nature of the TIR : TIR interactions in the respective signalosomes. Here, we review the well-studied TIR domain-containing proteins involved in eukaryotic immunity, focusing on the structures, interactions and their corresponding functional roles. Structurally, the signalosomes fall into two separate groups, the scaffold and enzyme TIR-domain assemblies, both of which feature open-ended complexes with two strands of TIR domains, but differ in the orientation of the two strands. We compare and contrast how TIR domains assemble and signal through distinct scaffolding and enzymatic roles, ultimately leading to distinct cellular innate-immunity and cell-death outcomes.
TIR（Toll/interleukin-1 受体/抵抗蛋白）结构域广泛存在于动植物中，是先天免疫系统的重要组成部分。TIR 结构域在信号转导中的一个关键特征是其弱而短暂的自身缔合和与其他 TIR 结构域的缔合。随着最近发现几个 TIR 结构域具有 NAD-核苷酶活性，TIR 结构域作为催化酶的新作用已被确立，这些 TIR 结构域主要参与细胞死亡途径。尽管在这两种情况下 TIR 结构域的自身缔合都是必需的，但 TIR 结构域的功能特异性部分与相应信号小体中 TIR: TIR 相互作用的性质有关。在这里，我们回顾了参与真核免疫的研究充分的 TIR 结构域蛋白，重点介绍了它们的结构、相互作用及其相应的功能作用。从结构上讲，信号小体分为两组，支架和酶 TIR 结构域组装体，它们都具有两个 TIR 结构域链的开放式复合物，但两个链的取向不同。我们比较和对比了 TIR 结构域如何通过不同的支架和酶作用组装和信号转导，最终导致不同的细胞先天免疫和细胞死亡结果。
