A tale of two domains - a structural perspective of the pseudokinase, MLKL

Abstract

Recently, the programmed necrosis or 'necroptosis' cell death pathway has attracted much interest because of its implication in multiple pathologies, including inflammatory diseases and the cell death arising from ischaemia reperfusion injuries. Pharmacologically, necroptosis is an attractive target because, unlike the counterpart pathway, apoptosis, it is dispensable for mammalian development. In particular, the most terminal-known obligate effector in the necroptosis pathway, the pseudokinase MLKL (mixed lineage kinase domain-like), holds particular appeal because, thus far, its only known function is as a mediator of necroptotic cell death. We review the current understanding and gaps in ..