학술논문
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis
Document Type
article
Author
Sarah E. Garnish; Yanxiang Meng; Akiko Koide; Jarrod J. Sandow; Eric Denbaum; Annette V. Jacobsen; Wayland Yeung; Andre L. Samson; Christopher R. Horne; Cheree Fitzgibbon; Samuel N. Young; Phoebe P. C. Smith; Andrew I. Webb; Emma J. Petrie; Joanne M. Hildebrand; Natarajan Kannan; Peter E. Czabotar; Shohei Koide; James M. Murphy
Source
Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
Subject
Language
English
ISSN
2041-1723
Abstract
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 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 induction of necroptosis.