Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain

ABSTRACT Two-component signaling systems (TCSs) function to detect environmental cues and transduce this information into a change in transcription. In its simplest form, TCS-dependent regulation of transcription entails phosphoryl-transfer from a sensory histidine kinase to its cognate DNA-binding...

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Autores principales:	Benjamin J. Stein, Aretha Fiebig, Sean Crosson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Caulobacter crescentus Fe-S FixL FixT feedback inhibition hypoxia Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/96f5cea7571b48868a02e10d654b0463
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spelling	oai:doaj.org-article:96f5cea7571b48868a02e10d654b04632021-11-15T15:57:01ZFeedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain10.1128/mBio.03383-192150-7511https://doaj.org/article/96f5cea7571b48868a02e10d654b04632020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03383-19https://doaj.org/toc/2150-7511ABSTRACT Two-component signaling systems (TCSs) function to detect environmental cues and transduce this information into a change in transcription. In its simplest form, TCS-dependent regulation of transcription entails phosphoryl-transfer from a sensory histidine kinase to its cognate DNA-binding receiver protein. However, in certain cases, auxiliary proteins may modulate TCSs in response to secondary environmental cues. Caulobacter crescentus FixT is one such auxiliary regulator. FixT is composed of a single receiver domain and functions as a feedback inhibitor of the FixL-FixJ (FixLJ) TCS, which regulates the transcription of genes involved in adaptation to microaerobiosis. We sought to define the impact of fixT on Caulobacter cell physiology and to understand the molecular mechanism by which FixT represses FixLJ signaling. fixT deletion results in excess production of porphyrins and premature entry into stationary phase, demonstrating the importance of feedback inhibition of the FixLJ signaling system. Although FixT is a receiver domain, it does not affect dephosphorylation of the oxygen sensor kinase FixL or phosphoryl-transfer from FixL to its cognate receiver FixJ. Rather, FixT represses FixLJ signaling by inhibiting the FixL autophosphorylation reaction. We have further identified a 4-cysteine motif in Caulobacter FixT that binds an Fe-S cluster and protects the protein from degradation by the Lon protease. Our data support a model in which the oxidation of this Fe-S cluster promotes the degradation of FixT in vivo. This proteolytic mechanism facilitates clearance of the FixT feedback inhibitor from the cell under normoxia and resets the FixLJ system for a future microaerobic signaling event. IMPORTANCE Two-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components, a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that a single-domain receiver protein, FixT, binds an Fe-S cluster and controls Caulobacter heme homeostasis though its function as a negative-feedback regulator of the oxygen sensor kinase FixL. We provide evidence that the Fe-S cluster protects FixT from Lon-dependent proteolysis in the cell and endows FixT with the ability to function as a second, autonomous oxygen/redox sensor in the FixL-FixJ signaling pathway. This study introduces a novel mechanism of regulated TCS feedback control by an Fe-S-binding receiver domain.Benjamin J. SteinAretha FiebigSean CrossonAmerican Society for MicrobiologyarticleCaulobacter crescentusFe-SFixLFixTfeedback inhibitionhypoxiaMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caulobacter crescentus Fe-S FixL FixT feedback inhibition hypoxia Microbiology QR1-502
spellingShingle	Caulobacter crescentus Fe-S FixL FixT feedback inhibition hypoxia Microbiology QR1-502 Benjamin J. Stein Aretha Fiebig Sean Crosson Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
description	ABSTRACT Two-component signaling systems (TCSs) function to detect environmental cues and transduce this information into a change in transcription. In its simplest form, TCS-dependent regulation of transcription entails phosphoryl-transfer from a sensory histidine kinase to its cognate DNA-binding receiver protein. However, in certain cases, auxiliary proteins may modulate TCSs in response to secondary environmental cues. Caulobacter crescentus FixT is one such auxiliary regulator. FixT is composed of a single receiver domain and functions as a feedback inhibitor of the FixL-FixJ (FixLJ) TCS, which regulates the transcription of genes involved in adaptation to microaerobiosis. We sought to define the impact of fixT on Caulobacter cell physiology and to understand the molecular mechanism by which FixT represses FixLJ signaling. fixT deletion results in excess production of porphyrins and premature entry into stationary phase, demonstrating the importance of feedback inhibition of the FixLJ signaling system. Although FixT is a receiver domain, it does not affect dephosphorylation of the oxygen sensor kinase FixL or phosphoryl-transfer from FixL to its cognate receiver FixJ. Rather, FixT represses FixLJ signaling by inhibiting the FixL autophosphorylation reaction. We have further identified a 4-cysteine motif in Caulobacter FixT that binds an Fe-S cluster and protects the protein from degradation by the Lon protease. Our data support a model in which the oxidation of this Fe-S cluster promotes the degradation of FixT in vivo. This proteolytic mechanism facilitates clearance of the FixT feedback inhibitor from the cell under normoxia and resets the FixLJ system for a future microaerobic signaling event. IMPORTANCE Two-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components, a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that a single-domain receiver protein, FixT, binds an Fe-S cluster and controls Caulobacter heme homeostasis though its function as a negative-feedback regulator of the oxygen sensor kinase FixL. We provide evidence that the Fe-S cluster protects FixT from Lon-dependent proteolysis in the cell and endows FixT with the ability to function as a second, autonomous oxygen/redox sensor in the FixL-FixJ signaling pathway. This study introduces a novel mechanism of regulated TCS feedback control by an Fe-S-binding receiver domain.
format	article
author	Benjamin J. Stein Aretha Fiebig Sean Crosson
author_facet	Benjamin J. Stein Aretha Fiebig Sean Crosson
author_sort	Benjamin J. Stein
title	Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
title_short	Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
title_full	Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
title_fullStr	Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
title_full_unstemmed	Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
title_sort	feedback control of a two-component signaling system by an fe-s-binding receiver domain
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/96f5cea7571b48868a02e10d654b0463
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Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain

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