Evolution of protein kinase substrate recognition at the active site

by David Bradley, Pedro Beltrao

Protein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few residues near the phospho-acceptor residue, forming the so-called kinase-substrate motif. Kinases have b een extensively duplicated throughout evolution, but little is known about when in time new target motifs have arisen. Here, we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity-determining residues. We then analysed kinase specificity mo dels, based on known target sites, observing that specificity has remained mostly unchanged for recent kinase duplications. Finally, analysis of phosphorylation data from a taxonomically broad set of 48 eukaryotic species indicates that most phosphorylation motifs are broadly distributed in eukaryot es but are not present in prokaryotes. Overall, our results suggest that the set of eukaryotes kinase motifs present today was acquired around the time of the eukaryotic last common ancestor and that early expansions of the protein kinase fold rapidly explored the space of possible target motifs.

Source: PLoS Biology: Archived Table of Contents - June 23, 2019 Category: Biology Authors: David Bradley Source Type: research