Flicking the molecular switch underlying MLKL-mediated necroptosis.
The pseudokinase domain of the necroptosis effector mixed lineage kinase domain-like (MLKL) functions as a latch to restrain the unleashing of its N-terminal 4-helix bundle (4HB) domain. Cell death mediated by the 4HB domain relies on membrane association and oligomerization, which can be inhibited by an ATP-mimetic small molecule that binds the pseudokinase domain of MLKL.
Cell Signalling and Cell Death Division; The Walter and Eliza Hall Institute of Medical Research; Parkville, Australia; Department of Medical Biology; University of Melbourne; Parkville, Victoria, Australia.
Joanne M
JM
Hildebrand
Department of Medical Biology; University of Melbourne; Parkville, Victoria, Australia; ACRF Chemical Biology Division; The Walter and Eliza Hall Institute of Medical Research; Parkville, Australia.
Isabelle S
IS
Lucet
Cell Signalling and Cell Death Division; The Walter and Eliza Hall Institute of Medical Research; Parkville, Australia; Department of Medical Biology; University of Melbourne; Parkville, Victoria, Australia.
James M
JM
Murphy