Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL

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 Å 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.

Source: BJ Signal - November 13, 2013 Category: Biochemistry Authors: J M. Murphy, I S. Lucet, J M. Hildebrand, M C. Tanzer, S N. Young, P Sharma, G Lessene, W S. Alexander, J J. Babon, J Silke, P E. Czabotar Tags: BJ Biomolecules Source Type: research