Journal article

Flicking the molecular switch underlying MLKL-mediated necroptosis

JM Hildebrand, IS Lucet, JM Murphy

Molecular and Cellular Oncology | TAYLOR & FRANCIS INC | Published : 2015

Open access

Abstract

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.

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

This work was supported by a National Health and Medical Research Council fellowship to JMH, project 1057905 to JMM and ISL, and an Australian Research Council fellowship (FT100100100) to JMM. Additional support was obtained from the Australian Cancer Research Foundation, Victorian State Government Operational Infrastructure Support and NHMRC IRIISS grant (361646).