The Treponema pallidum tro Operon Encodes a Multiple Metal Transporter, a Zinc-dependent Transcriptional Repressor, and a Semi-autonomously Expressed Phosphoglycerate Mutase

The Treponema pallidum tro operon encodes an ABC transporter (TroABCD), a transcriptional repressor (TroR), and the essential glycolytic enzyme phosphoglycerate mutase (Gpm). The apparently discordant observations that the solute binding protein (TroA) binds Zn2+, whereas DNA binding by TroR in vitr...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2003-06, Vol.278 (23), p.20687-20694
Main Authors: Hazlett, Karsten R.O., Rusnak, Frank, Kehres, David G., Bearden, Scott W., La Vake, Carson J., La Vake, Morgan E., Maguire, Michael E., Perry, Robert D., Radolf, Justin D.
Format: Article
Language:English
Subjects:
Animals
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
Bacterial Proteins
Dose-Response Relationship, Drug
Escherichia coli
gpm gene
Manganese - metabolism
Manganese - pharmacology
Operon - drug effects
Operon - physiology
Periplasmic Binding Proteins - genetics
Periplasmic Binding Proteins - metabolism
Phosphoglycerate Mutase - genetics
Phosphoglycerate Mutase - metabolism
Rabbits
Repressor Proteins - genetics
Repressor Proteins - metabolism
Syphilis - microbiology
Transcription, Genetic - physiology
Treponema pallidum
Treponema pallidum - enzymology
Treponema pallidum - genetics
tro gene
TroA protein
TroR protein
Zinc - metabolism
Zinc - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The Treponema pallidum tro operon encodes an ABC transporter (TroABCD), a transcriptional repressor (TroR), and the essential glycolytic enzyme phosphoglycerate mutase (Gpm). The apparently discordant observations that the solute binding protein (TroA) binds Zn2+, whereas DNA binding by TroR in vitro is Mn2+-dependent, have generated uncertainty regarding the identities of the ligand(s) and co-repressor(s) of the permease. Moreover, this operonic structure suggests that Gpm expression, and hence glycolysis, the sole source of ATP for the bacterium, would be suspended during TroR-mediated repression. To resolve these discrepancies, we devised an experimental strategy permitting a more direct assessment of Tro operon function and regulation. We report that (i) apo-TroA has identical affinities for Zn2+ and Mn2+; (ii) the Tro transporter expressed in Escherichia coli imports Zn2+, Mn2+, and possibly iron; (iii) TroR represses transporter expression in E. coli at significantly lower concentrations of Zn2+ than of Mn2+; and (iv) TroR-mediated repression causes a disproportionately greater down-regulation of the transporter genes than of gpm. The much higher concentrations of Zn2+ than of Mn2+ in human body fluids suggests that Zn2+ is both the primary substrate and co-repressor of the permease in vivo. Our data also indicate that Gpm expression and, therefore, glycolysis would not be abrogated when T. pallidum encounters high Zn2+ levels.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M300781200