Structural highlights
Function
MLKL_HUMAN Required for the execution of programmed necrosis.[1]
Publication Abstract from PubMed
The pseudokinase, Mixed lineage kinase domain-like (MLKL), was recently identified as an essential checkpoint in the programmed necrosis or "necroptosis" cell death pathway. Here, we present the crystal structure of the human MLKL pseudokinase domain at 1.7 A 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, our study provides insights into the evolution of nucleotide binding mechanisms amongst pseudokinases and their mechanistic divergence from conventional, catalytically-active protein kinases.
Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL.,Murphy JM, Lucet IS, Hildebrand JM, Tanzer MC, Young SN, Sharma P, Lessene G, Alexander WS, Babon JJ, Silke J, Czabotar PE Biochem J. 2013 Nov 13. PMID:24219132[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012 Jan 20;148(1-2):228-43. doi: 10.1016/j.cell.2011.11.030. PMID:22265414 doi:http://dx.doi.org/10.1016/j.cell.2011.11.030
- ↑ Murphy JM, Lucet IS, Hildebrand JM, Tanzer MC, Young SN, Sharma P, Lessene G, Alexander WS, Babon JJ, Silke J, Czabotar PE. Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL. Biochem J. 2013 Nov 13. PMID:24219132 doi:http://dx.doi.org/10.1042/BJ20131270
