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- Title
Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL.
- Authors
MURPHY, James M.; LUCET, Isabelle S.; HILDEBRAND, Joanne M.; TANZER, Maria C.; YOUNG, Samuel N.; SHARMA, Pooja; LESSENE, Guillaume; ALEXANDER, Warren S.; BABON, Jeffrey J.; SILKE, John; CZABOTAR, Peter E.
- Abstract
The pseudokinase MLKL(mixed lineage kinase domain-like)was identified recently as an essential checkpoint in the programmed necrosis or 'necroptosis' cell death pathway. In the present study, we report the crystal structure of the human MLKL pseudokinase domain at 1.7 Å (1 Å=0.1 nm) resolution and probe its nucleotide-binding mechanism by performing structure-based mutagenesis. By comparing the structures and nucleotide-binding determinants of human and mouse MLKL orthologues, the present study provides insights into the evolution of nucleotidebinding mechanisms among pseudokinases and their mechanistic divergence from conventional catalytically active protein kinases.
- Subjects
CRYSTAL structure; PROTEIN kinases; APOPTOSIS; MUTAGENESIS; BIOLOGICAL divergence; PROTEIN-protein interactions; MAMMALS
- Publication
Biochemical Journal, 2014, Vol 457, Issue 3, p369
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20131270