Cleavage of a putative metal permease in Chlamydia trachomatis yields an iron-dependent transcriptional repressor.
The regulation of iron homeostasis is essential for most organisms, because iron is required for a variety of conserved biochemical processes, yet can be toxic at high concentrations. Upon experiencing iron starvation in vitro, the obligate intracellular human pathogen Chlamydia trachomatis exhibits elevated expression of a putative iron-transport system encoded by the ytg operon. The third component of the ytg operon, CT069 (YtgCR), encodes a protein with two distinct domains: a membrane-anchored metal ion permease and a diphtheria toxin repressor (DtxR)-like transcriptional repressor. In this report, we demonstrate that the C-terminal domain of CT069 (YtgR) serves as an iron-dependent autorepressor of the ytg operon. Moreover, the nascent full-length metal permease-transcriptional repressor protein was processed during the course of infection, and heterologously when expressed in Escherichia coli. The products produced by heterologous cleavage in E. coli were functional in the repression of a reporter gene downstream of a putative YtgR operator. We report a bona fide mechanism of iron-dependent regulation of transcription in Chlamydia. Moreover, the unusual membrane permease-DNA-binding polypeptide fusion configuration was found in several bacteria. Therefore, the DNA-binding capability and liberation of the YtgR domain from a membrane-anchored permease in C. trachomatis could represent a previously uncharacterized mechanism for prokaryotic regulation of iron-homeostasis.
Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology,  Imperial College, London SW7 2AZ,  United Kingdom.
Christopher C
CC
Thompson
Sophie S
SS
Nicod
Denise S
DS
Malcolm
Scott S
SS
Grieshaber
Rey A
RA
Carabeo
D000595:Amino Acid Sequence; D002692:Chlamydia trachomatis / Q000201:enzymology*; D007501:Iron / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009876:Operon; D059748:Proteolysis; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D012097:Repressor Proteins; D007501:Iron