RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. 
Here, we report that the RIP homotypic interaction motifs (RHIMs) of RIP1 and 
RIP3 mediate the assembly of heterodimeric filamentous structures. The fibrils 
exhibit classical characteristics of β-amyloids, as shown by Thioflavin T (ThT) 
and Congo red (CR) binding, circular dichroism, infrared spectroscopy, X-ray 
diffraction, and solid-state NMR. Structured amyloid cores are mapped in RIP1 
and RIP3 that are flanked by regions of mobility. The endogenous RIP1/RIP3 
complex isolated from necrotic cells binds ThT, is ultrastable, and has a 
fibrillar core structure, whereas necrosis is partially inhibited by ThT, CR, 
and another amyloid dye, HBX. Mutations in the RHIMs of RIP1 and RIP3 that are 
defective in the interaction compromise cluster formation, kinase activation, 
and programmed necrosis in vivo. The current study provides insight into the 
structural changes that occur when RIP kinases are triggered to execute 
different signaling outcomes and expands the realm of amyloids to complex 
formation and signaling.