The structural basis of necroptotic cell death signaling
Journal Title
Trends Biochem Sci
Publication Type
Journal Article in press
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 necroptotic signaling. Structural studies have played a key role in establishing models that describe MLKL's transition from a dormant monomer to a killer oligomer and revealing important interspecies differences.
Publisher
Cell Press
Research Division(s)
Structural Biology; Cell Signalling And Cell Death
PubMed ID
30509860
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-12-18 02:54:30
Last Modified: 2018-12-18 04:17:08
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