CSIRO Plant Industry, Canberra, Australian Capital Territory 2601, Australia.
School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Infectious Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
Cell Host Microbe. 2011 Mar 17;9(3):200-211. doi: 10.1016/j.chom.2011.02.009.
The Toll/interleukin-1 receptor (TIR) domain occurs in animal and plant immune receptors. In the animal Toll-like receptors, homodimerization of the intracellular TIR domain is required for initiation of signaling cascades leading to innate immunity. By contrast, the role of the TIR domain in cytoplasmic nucleotide-binding/leucine-rich repeat (NB-LRR) plant immune resistance proteins is poorly understood. L6 is a TIR-NB-LRR resistance protein from flax (Linum usitatissimum) that confers resistance to the flax rust phytopathogenic fungus (Melampsora lini). We determine the crystal structure of the L6 TIR domain and show that, although dispensable for pathogenic effector protein recognition, the TIR domain alone is both necessary and sufficient for L6 immune signaling. We demonstrate that the L6 TIR domain self-associates, most likely forming a homodimer. Analysis of the structure combined with site-directed mutagenesis suggests that self-association is a requirement for immune signaling and reveals distinct surface regions involved in self-association, signaling, and autoregulation.
Toll/白细胞介素-1 受体 (TIR) 结构域存在于动物和植物的免疫受体中。在动物的 Toll 样受体中，细胞内 TIR 结构域的同源二聚化是启动导致先天免疫的信号级联所必需的。相比之下，细胞质核苷酸结合/富含亮氨酸重复 (NB-LRR) 植物免疫抗性蛋白中 TIR 结构域的作用知之甚少。L6 是来自亚麻（Linum usitatissimum）的 TIR-NB-LRR 抗性蛋白，赋予其对亚麻锈病病原菌（Melampsora lini）的抗性。我们确定了 L6 TIR 结构域的晶体结构，并表明尽管对致病性效应蛋白识别不重要，但 TIR 结构域本身对于 L6 免疫信号是必需且充分的。我们证明了 L6 TIR 结构域自身缔合，很可能形成同源二聚体。结构分析与定点突变相结合表明，自身缔合是免疫信号的要求，并揭示了参与自身缔合、信号转导和自身调节的不同表面区域。
