The RHIM domain of RIPK1, a master regulator of cell death and inflammation, forms functional amyloid assemblies whose atomic structure remained elusive until now.

In this study, led by the biosolids NMR group, reveal for the first time the three-dimensional architecture of RIPK1 amyloids using an integrative approach combining solid-state NMR and cryo-electron microscopy. The authors show that the amyloid core of RIPK1 consists of a zigzag β-sheet architecture stabilized by a precise hydrogen-bonding network. This structural arrangement accounts for both the stability and the molecular specificity of the assembly as a signaling platform. The structure was determined at the Manuel Rico Laboratory (IQF-CSIC, Madrid) using a state-of-the-art 600 MHz solid-state NMR spectrometer, the only one of its kind in Europe, and part of the Spanish ICTS Biomolecular NMR Laboratory Network (R-LRB). This study reports the first structure resolved in Spain using solid-state NMR, a technique of growing relevance in structural biology. It marks a key step in establishing the ICTS R-LRB as a leading facility for studying protein assemblies and offers new insights into how functional RIPK1 assembly may shift toward pathological processes in human disease. Reference: Polonio et al. (2025) Structural basis for amyloid fibril assembly by the master cell-signaling regulator RIPK1. Nature Communications. https://www.nature.com/articles/s41467-025-64621-6