Core of the partner switching signalling mechanism is conserved in the obligate intracellular pathogen Chlamydia trachomatis - PubMed (original) (raw)
Core of the partner switching signalling mechanism is conserved in the obligate intracellular pathogen Chlamydia trachomatis
Lei Hua et al. Mol Microbiol. 2006 Jan.
Free article
Abstract
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that can cause sexually transmitted and ocular diseases in humans. Its biphasic developmental cycle and ability to evade host-cell defences suggest that the organism responds to external signals, but its genome encodes few recognized signalling pathways. One such pathway is predicted to function by a partner switching mechanism, in which key protein interactions are controlled by serine phosphorylation. From genome analysis this mechanism is both ancient and widespread among eubacteria, but it has been experimentally characterized in only a few. C. trachomatis has no system of genetic exchange, so here an in vitro approach was used to establish the activities and interactions of the inferred partner switching components: the RsbW switch protein/kinase and its RsbV antagonists. The C. trachomatis genome encodes two RsbV paralogs, RsbV(1) and RsbV(2). We found that each RsbV protein was specifically phosphorylated by RsbW, and tandem mass spectrometry located the phosphoryl group on a conserved serine residue. Mutant RsbV(1) and RsbV(2) proteins in which this conserved serine was changed to alanine could activate the yeast two-hybrid system when paired with RsbW, whereas mutant proteins bearing a charged aspartate failed to activate. From this we infer that the phosphorylation state of RsbV(1) and RsbV(2) controls their interaction with RsbW in vivo. This experimental demonstration that the core of the partner switching mechanism is conserved in C. trachomatis indicates that its basic features are maintained over a large evolutionary span. Although the molecular target of the C. trachomatis switch remains to be identified, based on the predicted properties of its input phosphatases we propose that the pathway controls an important aspect of the developmental cycle within the host, in response to signals external to the C. trachomatis cytoplasmic membrane.
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