Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia.
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
IUCrJ. 2024 Sep 1;11(Pt 5):695-707. doi: 10.1107/S2052252524007693.
The TIR (Toll/interleukin-1 receptor) domain represents a vital structural element shared by proteins with roles in immunity signalling pathways across phyla (from humans and plants to bacteria). Decades of research have finally led to identifying the key features of the molecular basis of signalling by these domains, including the formation of open-ended (filamentous) assemblies (responsible for the signalling by cooperative assembly formation mechanism, SCAF) and enzymatic activities involving the cleavage of nucleotides. We present a historical perspective of the research that led to this understanding, highlighting the roles that different structural methods played in this process: X-ray crystallography (including serial crystallography), microED (micro-crystal electron diffraction), NMR (nuclear magnetic resonance) spectroscopy and cryo-EM (cryogenic electron microscopy) involving helical reconstruction and single-particle analysis. This perspective emphasizes the complementarity of different structural approaches.
TIR（Toll/白细胞介素-1 受体）结构域是一个重要的结构元件，存在于不同生物门（从人类和植物到细菌）的免疫信号通路蛋白中。经过几十年的研究，终于确定了这些结构域信号转导分子基础的关键特征，包括开放式（丝状）组装的形成（负责通过合作组装形成机制 SCAF 进行信号转导）和涉及核苷酸切割的酶活性。我们展示了导致这种理解的研究的历史视角，强调了不同结构方法在这个过程中所扮演的角色：X 射线晶体学（包括连续晶体学）、微 ED（微晶体电子衍射）、NMR（核磁共振）光谱和 cryo-EM（低温电子显微镜），包括螺旋重建和单颗粒分析。这种观点强调了不同结构方法的互补性。
