Nimma Surekha, Ve Thomas, Williams Simon J, Kobe Bostjan
School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia.
Curr Opin Struct Biol. 2017 Apr;43:122-130. doi: 10.1016/j.sbi.2016.12.014. Epub 2017 Jan 13.
TIR (Toll/interleukin-1 receptor/resistance protein) domains feature in animal, plant and bacterial proteins involved in innate immunity pathways and associated processes. They function through protein:protein interactions, in particular self-association and homotypic association with other TIR domains. Structures of TIR domains from all phyla have been determined, but common association modes have only emerged for plant and bacterial TIR domains, and not for mammalian TIR domains. Numerous attempts involving hybrid approaches, which have combined structural, computational, mutagenesis and biophysical data, have failed to converge onto common models of how these domains associate and function. We propose that the available data can be reconciled in the context of higher-order assembly formation, and that TIR domains function through signaling by cooperative assembly formation (SCAF).
TIR（Toll/白细胞介素-1受体/抗性蛋白）结构域存在于参与天然免疫途径及相关过程的动物、植物和细菌蛋白质中。它们通过蛋白质与蛋白质的相互作用发挥功能，特别是与其他TIR结构域的自我缔合和同型缔合。已确定了所有门类的TIR结构域的结构，但仅在植物和细菌TIR结构域中出现了常见的缔合模式，而在哺乳动物TIR结构域中并未出现。许多涉及混合方法的尝试，将结构、计算、诱变和生物物理数据结合起来，都未能得出这些结构域如何缔合和发挥功能的通用模型。我们提出，现有数据可以在高阶组装形成的背景下得到协调，并且TIR结构域通过协同组装形成信号传导（SCAF）发挥功能。
