DosT and DevS are oxygen‐switched kinases in Mycobacterium tuberculosis
- 1 August 2007
- journal article
- Published by Wiley in Protein Science
- Vol. 16 (8), 1708-1719
- https://doi.org/10.1110/ps.072897707
Abstract
Exposure of Mycobacterium tuberculosis to hypoxia is known to alter the expression of many genes, including ones thought to be involved in latency, via the transcription factor DevR (also called DosR). Two sensory kinases, DosT and DevS (also called DosS), control the activity of DevR. We show that, like DevS, DosT contains a heme cofactor within an N-terminal GAF domain. For full-length DosT and DevS, we determined the ligand-binding parameters and the rates of ATP reaction with the liganded and unliganded states. In both proteins, the heme state was coupled to the kinase such that the unliganded, CO-bound, and NO-bound forms were active, but the O(2)-bound form was inactive. Oxygen-bound DosT was unusually inert to oxidation to the ferric state (half life in air >60 h). Though the kinase activity of DosT was unaffected by NO, this ligand bound 5000 times more avidly than O(2) to DosT (K(d) [NO] approximately 5 nM versus K(d) [O(2)] = 26 microM). These results demonstrate direct and specific O(2) sensing by proteins in M. tuberculosis and identify for the first time a signal ligand for a sensory kinase from this organism. They also explain why exposure of M. tuberculosis to NO donors under aerobic conditions can give results identical to hypoxia, i.e., NO saturates DosT, preventing O(2) binding and yielding an active kinase.Keywords
This publication has 67 references indexed in Scilit:
- The W-Beijing Lineage of Mycobacterium tuberculosis Overproduces Triglycerides and Has the DosR Dormancy Regulon Constitutively UpregulatedJournal of Bacteriology, 2007
- DevS, a Heme-Containing Two-Component Oxygen Sensor of Mycobacterium tuberculosisBiochemistry, 2007
- Expression of mycobacterial cell division protein, FtsZ, and dormancy proteins, DevR and Acr, within lung granulomas throughout guinea pig infectionFEMS Immunology & Medical Microbiology, 2006
- Dissecting virulence pathways of Mycobacterium tuberculosis through protein–protein associationProceedings of the National Academy of Sciences of the United States of America, 2006
- A GAF Domain in the Hypoxia/NO-inducible Mycobacterium tuberculosis DosS Protein Binds HaemJournal of Molecular Biology, 2005
- Cross talk between DevS sensor kinase homologue, Rv2027c, and DevR response regulator of Mycobacterium tuberculosisFEBS Letters, 2004
- Disparate Oxygen Responsiveness of Two Regulatory Cascades That Control Expression of Symbiotic Genes in Bradyrhizobium japonicumJournal of Bacteriology, 2003
- Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequenceNature, 1998
- High-Resolution Crystal Structures of Distal Histidine Mutants of Sperm Whale MyoglobinJournal of Molecular Biology, 1993
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970