Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor

ABSTRACT The anti-σ factor NepR plays a central role in regulation of the general stress response (GSR) in alphaproteobacteria. This small protein has two known interaction partners: its cognate extracytoplasmic function (ECF) σ factor and the anti-anti-σ factor, PhyR. Stress-dependent phosphorylati...

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Autores principales:	Julien Herrou, Jonathan W. Willett, Sean Crosson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/55bb4338a5784545bd6cab8ce0ab2ed9
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spelling	oai:doaj.org-article:55bb4338a5784545bd6cab8ce0ab2ed92021-11-15T15:41:27ZStructured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor10.1128/mBio.00910-152150-7511https://doaj.org/article/55bb4338a5784545bd6cab8ce0ab2ed92015-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00910-15https://doaj.org/toc/2150-7511ABSTRACT The anti-σ factor NepR plays a central role in regulation of the general stress response (GSR) in alphaproteobacteria. This small protein has two known interaction partners: its cognate extracytoplasmic function (ECF) σ factor and the anti-anti-σ factor, PhyR. Stress-dependent phosphorylation of PhyR initiates a protein partner switch that promotes phospho-PhyR binding to NepR, which frees ECF σ to activate transcription of genes required for cell survival under adverse or fluctuating conditions. We have defined key functional roles for structured and intrinsically disordered domains of Caulobacter crescentus NepR in partner binding and activation of GSR transcription. We further demonstrate that NepR strongly stimulates the rate of PhyR phosphorylation in vitro and that this effect requires the structured and disordered domains of NepR. This result provides evidence for an additional layer of GSR regulation in which NepR directly influences activation of its binding partner, PhyR, as an anti-anti-σ factor. We conclude that structured and intrinsically disordered domains of NepR coordinately control multiple functions in the GSR signaling pathway, including core protein partner switch interactions and pathway activation by phosphorylation. IMPORTANCE Anti-σ factors are key molecular participants in a range of adaptive responses in bacteria. The anti-σ factor NepR plays a vital role in a multiprotein partner switch that governs general stress response (GSR) transcription in alphaproteobacteria. We have defined conserved and unconserved features of NepR structure that determine its function as an anti-σ factor and uncovered a functional role for intrinsically disordered regions of NepR in partner binding events required for GSR activation. We further demonstrate a novel function for NepR as an enhancer of PhyR phosphorylation; this activity also requires the disordered domains of NepR. Our results provide evidence for a new layer of GSR regulatory control in which NepR directly modulates PhyR phosphorylation and, hence, activation of the GSR.Julien HerrouJonathan W. WillettSean CrossonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 4 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Julien Herrou Jonathan W. Willett Sean Crosson Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
description	ABSTRACT The anti-σ factor NepR plays a central role in regulation of the general stress response (GSR) in alphaproteobacteria. This small protein has two known interaction partners: its cognate extracytoplasmic function (ECF) σ factor and the anti-anti-σ factor, PhyR. Stress-dependent phosphorylation of PhyR initiates a protein partner switch that promotes phospho-PhyR binding to NepR, which frees ECF σ to activate transcription of genes required for cell survival under adverse or fluctuating conditions. We have defined key functional roles for structured and intrinsically disordered domains of Caulobacter crescentus NepR in partner binding and activation of GSR transcription. We further demonstrate that NepR strongly stimulates the rate of PhyR phosphorylation in vitro and that this effect requires the structured and disordered domains of NepR. This result provides evidence for an additional layer of GSR regulation in which NepR directly influences activation of its binding partner, PhyR, as an anti-anti-σ factor. We conclude that structured and intrinsically disordered domains of NepR coordinately control multiple functions in the GSR signaling pathway, including core protein partner switch interactions and pathway activation by phosphorylation. IMPORTANCE Anti-σ factors are key molecular participants in a range of adaptive responses in bacteria. The anti-σ factor NepR plays a vital role in a multiprotein partner switch that governs general stress response (GSR) transcription in alphaproteobacteria. We have defined conserved and unconserved features of NepR structure that determine its function as an anti-σ factor and uncovered a functional role for intrinsically disordered regions of NepR in partner binding events required for GSR activation. We further demonstrate a novel function for NepR as an enhancer of PhyR phosphorylation; this activity also requires the disordered domains of NepR. Our results provide evidence for a new layer of GSR regulatory control in which NepR directly modulates PhyR phosphorylation and, hence, activation of the GSR.
format	article
author	Julien Herrou Jonathan W. Willett Sean Crosson
author_facet	Julien Herrou Jonathan W. Willett Sean Crosson
author_sort	Julien Herrou
title	Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
title_short	Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
title_full	Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
title_fullStr	Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
title_full_unstemmed	Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
title_sort	structured and dynamic disordered domains regulate the activity of a multifunctional anti-σ factor
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/55bb4338a5784545bd6cab8ce0ab2ed9
work_keys_str_mv	AT julienherrou structuredanddynamicdisordereddomainsregulatetheactivityofamultifunctionalantisfactor AT jonathanwwillett structuredanddynamicdisordereddomainsregulatetheactivityofamultifunctionalantisfactor AT seancrosson structuredanddynamicdisordereddomainsregulatetheactivityofamultifunctionalantisfactor
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Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor

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