Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL
- Author(s)
- Murphy, JM; Lucet, IS; Hildebrand, JM; Tanzer, MC; Young, SN; Sharma, P; Lessene, G; Alexander, WS; Babon, JJ; Silke, J; Czabotar, PE;
- Details
- Publication Year 2014-02-01,Volume 457,Issue #3,Page 369-77
- Journal Title
- Biochemical Journal
- Publication Type
- Journal Article
- 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 A (1 A=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 nucleotide-binding mechanisms among pseudokinases and their mechanistic divergence from conventional catalytically active protein kinases.
- Publisher
- PORTLAND PRESS
- Research Division(s)
- Cancer And Haematology; Structural Biology; Chemical Biology; Cell Signalling And Cell Death
- Publisher's Version
- https://doi.org/10.1042/bj20131270
- NHMRC Grants
- NHMRC/637342, NHMRC/1016647, NHMRC/1046984,
- ARC Grants
- ARC/FT100100100, ARC/FT110100169, ARC/FT0992105,
- Terms of Use/Rights Notice
- © The Authors Journal compilation © 2014 Biochemical Society
Creation Date: 2014-01-17 08:17:12
Last Modified: 2015-03-24 12:20:10