Mechanistic Studies of MLKL Mediated Cell Death

Abstract

Necroptosis is a form of inflammatory programmed cell death. Thought to have evolved to combat pathogen infection, necroptosis can be triggered via signalling through pattern recognition receptors or cytokines from the TNF family. The final stages of necroptosis signalling are characterised by the kinase RIPK3 oligomerising with various RHIM domain containing proteins, which may assemble together into large functional amyloid complexes. Within these complexes RIPK3 is thought to auto-phosphorylate and then recruit and phosphorylate the final known effector of the pathway Mixed Lineage Kinase domain-Like protein (MLKL). Once the pseudokinase MLKL is phosphorylated, it transforms from an inert..