In:
The FEBS Journal, Wiley, Vol. 286, No. 21 ( 2019-11), p. 4278-4293
Abstract:
Tuberculosis is one of the oldest known infectious diseases, responsible for millions of deaths annually around the world. The ability of Mycobacterium tuberculosis (Mtb) to enter into a dormant state has been considered integral to the success of this bacterium as a human pathogen. One of the key systems involved in regulating the entrance into dormancy is the differentially expressed in virulent strain sensor protein (DevS) [(dormancy survival sensor protein (DosS)]. However, the physiological signal for DevS has remained unclear since it was first shown to be a heme‐based sensor with conflicting reports on whether it is a redox or an oxygen sensor. To address this question and provide a better understanding of the electronic properties of this protein, we present here, for the first time, a series of spectroelectrochemistry measurements of the full‐length holo DevS in anaerobic conditions as well as bound to CO, NO, imidazole (Imz), cyanide, and O 2 . An interesting feature of this protein is its ability to bind Imz even in the ferrous state, implying small‐molecule analogues could be designed as potential regulators. Nonetheless, a midpoint potential ( E m ) value of +10 mV [vs normal hydrogen electrode (NHE)] for DevS as measured under anaerobic conditions is much higher than the expected cytosolic potential for Mtb or even within stimulated macrophages (~ −270 mV vs NHE), indicating this sensor works in a reduced ferrous state. These data, along with the high oxygen affinity and very slow auto‐oxidation rate of DevS, provides evidence that it is not a redox sensor. Overall, this study validates the biological function of DevS as an oxygen sensor directly involved in the dormancy/latency of Mtb.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.v286.21
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2172518-4
SSG:
12
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