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Oxygen triggers signal transduction in the DevS (DosS) sensor of Mycobacterium tuberculosis by modulating the quaternary structure
Author(s) -
Lobão Josiane Bezerra da Silva,
Gondim Ana C. S.,
Guimarães Wellinson G.,
GillesGonzalez MarieAlda,
Lopes Luiz Gonzaga de França,
Sousa Eduardo H. S.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14734
Subject(s) - devs , protein quaternary structure , biophysics , biology , histidine kinase , mycobacterium tuberculosis , signal transduction , microbiology and biotechnology , chemistry , biochemistry , mutant , gene , protein subunit , tuberculosis , modeling and simulation , systems engineering , engineering , medicine , pathology
A major challenge to the control and eventual eradication of Mycobacterium tuberculosis infection is this pathogen's prolonged dormancy. The heme‐based oxygen sensor protein DevS (DosS) plays a key role in this phenomenon, because it is a major activator of the transcription factor DevR. When DevS is active, its histidine protein kinase region is ON and it phosphorylates and activates DevR, which can induce the transcription of the dormancy regulon genes. Here, we have investigated the mechanism by which the ligation of molecular oxygen to a heme‐binding domain in DevS switches OFF its histidine protein kinase region. To shed light on the oligomerization states of this protein and possible protein‐surfaces of interaction, we used analytical gel filtration, together with dynamic light scattering, fluorescence spectroscopy and chemical crosslinking. We found that DevS exists as three major species: an octamer, a tetramer and a dimer. These three states were observed for the concentration range between 0.5 and 20 μ m DevS, but not below 0.1 μ m . Levels of DevS in M. tuberculosis are expected to range from 5 to 26 μ m . When this histidine protein kinase was OFF , the DevS was mainly tetrameric and dimeric; by contrast, when the kinase was ON , the protein was predominantly octameric. The changes in quaternary structure were rapid upon binding to the physiological signal. This finding represents a novel strategy for switching the activity of a two‐component heme‐based sensor. An enhanced understanding of this process might potentially lead to the design of novel regulatory agents that target the multimer interfaces for treatment of latent tuberculosis.