Structural Evolution of the Protein Kinase-Like Superfamily

Abstract

The protein kanase famuy is Sarge and important, but it is only one family in a Sarger smperfamuy of homologous kinases that phosphorySate a variety of substrates arid piay important raies art all three superkirtgdoms of iife. We used a carefuliy constructed structural alignment of selected kinases as the basis for a study of the structurai evoîuition of the protests kinase-uke swperfamify. The comparison of structures reveafed a "universal core" domain consisting osify of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the yniversai core some kirsase structures daspaay rsotabae changes, whue stall retairsirsg esserstia! activity. Hence, the protesn kirsase-Sike superfamuy has yrsdergorse substantial structurai and sequence revision over [orsg evolutionary timescaies. We corjstructed a phyaogenetic tree for the superfamuy using a novei approach that aiiowed for the combination of ssqisersce and structure irsformatiors into a unified quantitative analysas. When considered against the backdrop of species distribution and other metrics, our tree provides a competing scenario for the deveiopment of the various kirsase families from a shared common ancestor. We propose that most of the so-caSfed "atypicaa kinases" are rsot intermittentiy derived from protein kinases, but rather diverged eaHy in evoiistion to form a distinct phyietic group. Within the atypkai kisiases, the amirsogaycoside artd chofirte kirsase families appear to share the cfosest reiatiorsship. These two famiises in turn appear to be the most caoseiy related to the protein kanase famiiy. in addition, our anaiysis suggests that the actin-fragmin kirsase, an atypica! protein kinase, is more cîoseiy reîated to the phosphoinositide-3 kinase famuy than to the protein kinase famuy. The two most divergent famines, -kinases and phosphatadyiinositoi phosphate kinases (PSPKsj, appear to have distinct evoiytionary histories. Whue the PfPKs probabSy bave an evolutionary refatiorsship with the rest of the kinase superfamify, the relationship appears to be very distant {arid perhaps indirect). Conversely, the a-kinases appear to be an exception to tbe scenario of eariy divergence for the atypical kinases: they apparently arose relatively recentay im eukaryotes. We present possible scenarios for the derivation of the a-kinases from an extant kinase foid. Copyright: ©2005 Scheeff and Bourne.