<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone

ABSTRACT The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. tuberculosis protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacte...

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Autores principales:	Samuel H. Becker, Kathrin Ulrich, Avantika Dhabaria, Beatrix Ueberheide, William Beavers, Eric P. Skaar, Lakshminarayan M. Iyer, L. Aravind, Ursula Jakob, K. Heran Darwin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Hsp70 Mycobacterium chaperone protein proteostasis tuberculosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f5ea186d359e44bc9800d53283f1b1a1
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spelling	oai:doaj.org-article:f5ea186d359e44bc9800d53283f1b1a12021-11-15T15:56:43Z<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone10.1128/mBio.01545-202150-7511https://doaj.org/article/f5ea186d359e44bc9800d53283f1b1a12020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01545-20https://doaj.org/toc/2150-7511ABSTRACT The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. tuberculosis protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacterial lineages and appears to function analogously to the well-characterized Escherichia coli redox-regulated chaperone Hsp33, despite a dissimilar protein sequence. Rv0991c is transcriptionally coregulated with hsp60 and hsp70 chaperone genes in M. tuberculosis, suggesting that Rv0991c functions with these chaperones in maintaining protein quality control. Supporting this hypothesis, we found that, like oxidized Hsp33, oxidized Rv0991c prevents the aggregation of a model unfolded protein in vitro and promotes its refolding by the M. tuberculosis Hsp70 chaperone system. Furthermore, Rv0991c interacts with DnaK and can associate with many other M. tuberculosis proteins. We therefore propose that Rv0991c, which we named “Ruc” (redox-regulated protein with unstructured C terminus), represents a founding member of a new chaperone family that protects M. tuberculosis and other species from proteotoxicity during oxidative stress. IMPORTANCE M. tuberculosis infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of M. tuberculosis biology. As in all cells, protein quality control is essential for the viability of M. tuberculosis, which likely faces proteotoxic stress within a host. Here, we identify an M. tuberculosis protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential M. tuberculosis Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability.Samuel H. BeckerKathrin UlrichAvantika DhabariaBeatrix UeberheideWilliam BeaversEric P. SkaarLakshminarayan M. IyerL. AravindUrsula JakobK. Heran DarwinAmerican Society for MicrobiologyarticleHsp70MycobacteriumchaperoneproteinproteostasistuberculosisMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hsp70 Mycobacterium chaperone protein proteostasis tuberculosis Microbiology QR1-502
spellingShingle	Hsp70 Mycobacterium chaperone protein proteostasis tuberculosis Microbiology QR1-502 Samuel H. Becker Kathrin Ulrich Avantika Dhabaria Beatrix Ueberheide William Beavers Eric P. Skaar Lakshminarayan M. Iyer L. Aravind Ursula Jakob K. Heran Darwin <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
description	ABSTRACT The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. tuberculosis protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacterial lineages and appears to function analogously to the well-characterized Escherichia coli redox-regulated chaperone Hsp33, despite a dissimilar protein sequence. Rv0991c is transcriptionally coregulated with hsp60 and hsp70 chaperone genes in M. tuberculosis, suggesting that Rv0991c functions with these chaperones in maintaining protein quality control. Supporting this hypothesis, we found that, like oxidized Hsp33, oxidized Rv0991c prevents the aggregation of a model unfolded protein in vitro and promotes its refolding by the M. tuberculosis Hsp70 chaperone system. Furthermore, Rv0991c interacts with DnaK and can associate with many other M. tuberculosis proteins. We therefore propose that Rv0991c, which we named “Ruc” (redox-regulated protein with unstructured C terminus), represents a founding member of a new chaperone family that protects M. tuberculosis and other species from proteotoxicity during oxidative stress. IMPORTANCE M. tuberculosis infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of M. tuberculosis biology. As in all cells, protein quality control is essential for the viability of M. tuberculosis, which likely faces proteotoxic stress within a host. Here, we identify an M. tuberculosis protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential M. tuberculosis Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability.
format	article
author	Samuel H. Becker Kathrin Ulrich Avantika Dhabaria Beatrix Ueberheide William Beavers Eric P. Skaar Lakshminarayan M. Iyer L. Aravind Ursula Jakob K. Heran Darwin
author_facet	Samuel H. Becker Kathrin Ulrich Avantika Dhabaria Beatrix Ueberheide William Beavers Eric P. Skaar Lakshminarayan M. Iyer L. Aravind Ursula Jakob K. Heran Darwin
author_sort	Samuel H. Becker
title	<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
title_short	<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
title_full	<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
title_fullStr	<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
title_full_unstemmed	<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone
title_sort	<named-content content-type="genus-species">mycobacterium tuberculosis</named-content> rv0991c is a redox-regulated molecular chaperone
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/f5ea186d359e44bc9800d53283f1b1a1
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<named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Rv0991c Is a Redox-Regulated Molecular Chaperone

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