All living cells must be able to detect danger, fight infection and decide when to trigger programmed cell death. Although these processes are central to immunity, many of the molecular mechanisms behind them are only now being uncovered. One important group of players are TIR (Toll/interleukin-1 receptor) domains, found across animals, plants and bacteria in proteins that mediate immune responses. Using a range of structural biology approaches, including cryogenic electron microscopy, microcrystal electron diffraction and serial femtosecond crystallography, we characterized the signalling assemblies formed by TIR domains. We found that many TIR domains act as enzymes that cleave nucleotides, and we used nuclear magnetic resonance to identify the signalling products they generate. These assemblies form filaments, and the resulting signalling mechanism, which is distinct from classical pathways, has been termed SCAF (signalling by cooperative assembly formation). This emerging mechanism may open new avenues for treating inflammatory disorders and bacterial infections, as well as for protecting plants from disease.
Towards a quantum internet
Prof. Dr. Stephanie Wehner Delft University of Technology, QuTech, Delft, The Netherlands
