Journal article
The Structural Basis of Necroptotic Cell Death Signaling
EJ Petrie, PE Czabotar, JM Murphy
Trends in Biochemical Sciences | ELSEVIER SCIENCE LONDON | Published : 2019
Abstract
The recent implication of the cell death pathway, necroptosis, in innate immunity and a range of human pathologies has led to intense interest in the underlying molecular mechanism. Unlike the better-understood apoptosis pathway, necroptosis is a caspase-independent pathway that leads to cell lysis and release of immunogens downstream of death receptor and Toll-like receptor (TLR) ligation. Here we review the role of recent structural studies of the core machinery of the pathway, the protein kinases receptor-interacting protein kinase (RIPK)1 and RIPK3, and the terminal effector, the pseudokinase mixed lineage kinase domain-like protein (MLKL), in shaping our mechanistic understanding of nec..
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Funding Acknowledgements
We thank the National Health and Medical Research Council of Australia for their support of our studies via fellowships to P. E.G. (1079700) and J.M.M. (1105754), project grants on this subject (1124735, 1124737), and infrastructure funding (IRIISS 9000433). We are grateful to the Victorian State Government Operational Infrastructure Scheme and to the Australian Synchrotron for enabling structural studies reviewed herein. We apologize to our colleagues whose work we were unable to cite owing to space restrictions.