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The DosS-DosT/DosR Mycobacterial Sensor System
Santhosh Sivaramakrishnan1, Paul R Ortiz de Montellano1
1Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94158, USA; santhosh.sivaramakrishnan@ucsf.edu.
Biosensors
|July 9, 2014
Summary
The DosS/DosT system regulates Mycobacterium tuberculosis dormancy. These heme sensors detect gases and potentially redox states, controlling gene expression for survival.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- The DosS/DosR two-component system regulates the entry of Mycobacterium tuberculosis into a dormant state.
- DosR is a DNA-binding protein activated by phosphorylation from DosS or DosT.
- DosT is a sensor protein closely related to DosS, also involved in DosR-mediated dormancy.
Purpose of the Study:
- To review the structure, biophysical properties, and function of the DosS/DosT heme sensors.
- To explore the proposed roles of DosS and DosT as gas and redox state sensors.
Main Methods:
- Review of existing literature on the DosS/DosT system.
- Analysis of structural and biophysical data for DosS and DosT.
- Discussion of functional studies related to gas and redox sensing.
Main Results:
- DosT acts as a gas sensor, activated by low oxygen, NO, or CO binding in its ferrous state.
- DosS functions similarly as a gas sensor, with some evidence suggesting a role in redox sensing.
- Phosphorylated DosR binding to DNA triggers the expression of approximately fifty dormancy-linked genes.
Conclusions:
- The DosS/DosT system is crucial for regulating mycobacterial dormancy.
- DosS and DosT are heme-containing sensors with distinct but overlapping functions in gas detection.
- Further research is needed to fully elucidate the mechanisms of DosS and DosT in sensing and dormancy regulation.
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