Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

Emma J Petrie; Jarrod J Sandowl; Annette Jacobsen; Brian J Smith; Michael DW Griffin; Isabelle S Lucet; Weiwen Dai; Samuel N Young; Maria C Tanzer; Ahmad Wardak; Lung-Yu Liang; Angus D Cowan; Joanne M Hildebrand; Wilhelmus JA Kersten; Guillaume Lessene; John Silke; Peter E Czabotar; Andrew Webb; James M Murphy

Journal article

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

Emma J Petrie, Jarrod J Sandowl, Annette Jacobsen, Brian J Smith, Michael DW Griffin, Isabelle S Lucet, Weiwen Dai, Samuel N Young, Maria C Tanzer, Ahmad Wardak, Lung-Yu Liang, Angus D Cowan, Joanne M Hildebrand, Wilhelmus JA Kersten, Guillaume Lessene, John Silke, Peter E Czabotar, Andrew Webb, James M Murphy

Nature Communications | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/s41467-018-04714-7

University of Melbourne Researchers

Peter Czabotar Author Medical Biology (W.E.H.I.)

Isabelle Lucet Author Medical Biology (W.E.H.I.)

Andrew Webb Author Medical Biology (W.E.H.I.)

Guillaume Lessene Author Medical Biology (W.E.H.I.)

Jarrod Sandow Author Medical Biology (W.E.H.I.)

Grants

Awarded by National Health and Medical Research Council

Awarded by Australian Research Council

Funding Acknowledgements

We thank staff at the Australian Synchrotron SAXS/WAXS and MX beamlines for assistance with data collection, the Collaborative Crystallisation Centre (Parkville) for assistance with protein crystallization, Patrick Hennessy for technical assistance and Adeline Robin for MX data collection. We acknowledge Australian Government Research Training Program Stipend Scholarship support to A.V.J. and a Victorian International Research Scholarship to M.C.T. We are grateful to the National Health and Medical Research Council for fellowship (G.L., 1117089; J.S., 1058190; P.E.C., 1079700; J.M.M., 1105754), grant (1057905; 1124735), and infrastructure (IRIISS 9000433) support; the Australian Research Council (Future Fellowship to M.D.W.G., FT140100544); Australian Cancer Research Foundation; and the Victorian Government Operational Infrastructure Support scheme.