The Toxoplasma Kinase ROP18: An Active Member of a Degenerate Family

Anthony P Sinai

doi:10.1371/journal.ppat.0030016

Abstract

Intracellular parasitism defines the most intimate of interactions between a pathogen and host. Inherent in this equation are the needs of the pathogen to enter the cell and establish a replication-permissive niche while neutralizing and subverting cellular defenses. The protozoan parasite Toxoplasma gondii is particularly adept at every stage of intracellular parasitism, which has contributed to its being among the most cosmopolitan parasites on the planet [1]. Toxoplasma is a member of the Apicomplexa, so noted by the presence of specialized cytoskeletal and secretory organelles (the apical complex) that play a critical role in invasion [2]. Most prominent among these secretory organelles are the club-shaped rhoptries [3,4]. Recent work, including a detailed cataloging of the rhoptry proteome [5], coupled with the availability of the T. gondii genome and gene expression data (http://www.ToxoDB.org; [6]), have resulted in new insights into rhoptry functions. Among the activities inferred from the analysis of the proteomic and genomic data was a family of predicted serine threonine kinases related to the rhoptry protein ROP2 [7]. While ROP2 and several other members of the ROP2 family retain “molecular fossils,” reflecting their ancestry as kinases, they do not possess kinase activity on account of degeneracy and deletions at key catalytic sites [7]. However, bioinfomatic and structural prediction studies reveal that two members, ROP16 and ROP18, do retain all the elements needed to classify them as true kinases [7].

Highlights

I ntracellular parasitism defines the most intimate of interactions between a pathogen and host
This characterization is timely given a pair of recent papers from the Boothroyd [9] and Sibley [10] laboratories identifying ROP18 as a critical contributor to virulence, a finding that represents the first virulence factor identified in Toxoplasma using classical forward genetic approaches
A somewhat surprising revelation regarding the provenance of ROP2 family suggests they have all evolved from a progenitor serine threonine kinase on the basis of the presence of key signature motifs [7]

Summary

Introduction

I ntracellular parasitism defines the most intimate of interactions between a pathogen and host. ROP2, the founding member of this family, is secreted to the PVM at the time of parasite invasion, where it is believed to establish itself as an integral membrane protein with its N-terminus exposed to the host cell cytoplasm [17].

Results

Conclusion