Necrosome

The necrosome is the signaling complex that executes necroptosis. It assembles when RIPK1 and RIPK3 bind one another through shared RHIM domains, triggering RIPK3 activation, which in turn phosphorylates the pseudokinase MLKL. Phosphorylated MLKL undergoes a conformational change, oligomerizes, and traffics to the plasma membrane, where it ultimately drives the membrane rupture characteristic of necroptotic death. The necrosome can also assemble downstream of pattern-recognition receptors such as TLR3/TLR4 (via the adaptor TRIF) or the nucleic acid sensor ZBP1, linking necroptosis to innate immune sensing of pathogens or endogenous nucleic acids.