CONFORMATIONAL INTERCONVERSION OF MLKL AND DISENGAGEMENT FROM RIPK3 PRECEDE CELL DEATH BY NECROPTOSIS

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis

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Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis.Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed Cramp Bark them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations.By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the Defrost Fuse induction of necroptosis.

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