TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei

ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Samar Aramin [verfasserIn] Rosi Fassler [verfasserIn] Vaibhav Chikne [verfasserIn] Mor Goldenberg [verfasserIn] Tal Arian [verfasserIn] Liat Kolet Eliaz [verfasserIn] Oded Rimon [verfasserIn] Oren Ram [verfasserIn] Shulamit Michaeli [verfasserIn] Dana Reichmann [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone

Übergeordnetes Werk:	In: Frontiers in Microbiology - Frontiers Media S.A., 2011, 11(2020)
Übergeordnetes Werk:	volume:11 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmicb.2020.01844

Katalog-ID:	DOAJ048775800

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spelling	10.3389/fmicb.2020.01844 doi (DE-627)DOAJ048775800 (DE-599)DOAJb91bef5aaf77457cb479433f948516bc DE-627 ger DE-627 rakwb eng QR1-502 Samar Aramin verfasserin aut TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting. Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone Microbiology Rosi Fassler verfasserin aut Vaibhav Chikne verfasserin aut Mor Goldenberg verfasserin aut Tal Arian verfasserin aut Liat Kolet Eliaz verfasserin aut Oded Rimon verfasserin aut Oren Ram verfasserin aut Shulamit Michaeli verfasserin aut Dana Reichmann verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.01844 kostenfrei https://doaj.org/article/b91bef5aaf77457cb479433f948516bc kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.01844/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfields_unstemmed	10.3389/fmicb.2020.01844 doi (DE-627)DOAJ048775800 (DE-599)DOAJb91bef5aaf77457cb479433f948516bc DE-627 ger DE-627 rakwb eng QR1-502 Samar Aramin verfasserin aut TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting. Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone Microbiology Rosi Fassler verfasserin aut Vaibhav Chikne verfasserin aut Mor Goldenberg verfasserin aut Tal Arian verfasserin aut Liat Kolet Eliaz verfasserin aut Oded Rimon verfasserin aut Oren Ram verfasserin aut Shulamit Michaeli verfasserin aut Dana Reichmann verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.01844 kostenfrei https://doaj.org/article/b91bef5aaf77457cb479433f948516bc kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.01844/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsGer	10.3389/fmicb.2020.01844 doi (DE-627)DOAJ048775800 (DE-599)DOAJb91bef5aaf77457cb479433f948516bc DE-627 ger DE-627 rakwb eng QR1-502 Samar Aramin verfasserin aut TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting. Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone Microbiology Rosi Fassler verfasserin aut Vaibhav Chikne verfasserin aut Mor Goldenberg verfasserin aut Tal Arian verfasserin aut Liat Kolet Eliaz verfasserin aut Oded Rimon verfasserin aut Oren Ram verfasserin aut Shulamit Michaeli verfasserin aut Dana Reichmann verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.01844 kostenfrei https://doaj.org/article/b91bef5aaf77457cb479433f948516bc kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.01844/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsSound	10.3389/fmicb.2020.01844 doi (DE-627)DOAJ048775800 (DE-599)DOAJb91bef5aaf77457cb479433f948516bc DE-627 ger DE-627 rakwb eng QR1-502 Samar Aramin verfasserin aut TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting. Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone Microbiology Rosi Fassler verfasserin aut Vaibhav Chikne verfasserin aut Mor Goldenberg verfasserin aut Tal Arian verfasserin aut Liat Kolet Eliaz verfasserin aut Oded Rimon verfasserin aut Oren Ram verfasserin aut Shulamit Michaeli verfasserin aut Dana Reichmann verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.01844 kostenfrei https://doaj.org/article/b91bef5aaf77457cb479433f948516bc kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.01844/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
language	English
source	In Frontiers in Microbiology 11(2020) volume:11 year:2020
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topic_facet	Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone Microbiology
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container_title	Frontiers in Microbiology
authorswithroles_txt_mv	Samar Aramin @@aut@@ Rosi Fassler @@aut@@ Vaibhav Chikne @@aut@@ Mor Goldenberg @@aut@@ Tal Arian @@aut@@ Liat Kolet Eliaz @@aut@@ Oded Rimon @@aut@@ Oren Ram @@aut@@ Shulamit Michaeli @@aut@@ Dana Reichmann @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Samar Aramin
spellingShingle	Samar Aramin misc QR1-502 misc Hsp33 misc redox regulation misc redox regulation in T. brucei misc stress-regulated chaperones misc holdase chaperone misc Microbiology TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei
authorStr	Samar Aramin
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topic_title	QR1-502 TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei Hsp33 redox regulation redox regulation in T. brucei stress-regulated chaperones holdase chaperone
topic	misc QR1-502 misc Hsp33 misc redox regulation misc redox regulation in T. brucei misc stress-regulated chaperones misc holdase chaperone misc Microbiology
topic_unstemmed	misc QR1-502 misc Hsp33 misc redox regulation misc redox regulation in T. brucei misc stress-regulated chaperones misc holdase chaperone misc Microbiology
topic_browse	misc QR1-502 misc Hsp33 misc redox regulation misc redox regulation in T. brucei misc stress-regulated chaperones misc holdase chaperone misc Microbiology
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hierarchy_parent_title	Frontiers in Microbiology
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title	TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei
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title_full	TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei
author_sort	Samar Aramin
journal	Frontiers in Microbiology
journalStr	Frontiers in Microbiology
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author_browse	Samar Aramin Rosi Fassler Vaibhav Chikne Mor Goldenberg Tal Arian Liat Kolet Eliaz Oded Rimon Oren Ram Shulamit Michaeli Dana Reichmann
container_volume	11
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author-letter	Samar Aramin
doi_str_mv	10.3389/fmicb.2020.01844
author2-role	verfasserin
title_sort	trypox, a novel eukaryotic homolog of the redox-regulated chaperone hsp33 in trypanosoma brucei
callnumber	QR1-502
title_auth	TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei
abstract	ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting.
abstractGer	ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting.
abstract_unstemmed	ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting.
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title_short	TrypOx, a Novel Eukaryotic Homolog of the Redox-Regulated Chaperone Hsp33 in Trypanosoma brucei
url	https://doi.org/10.3389/fmicb.2020.01844 https://doaj.org/article/b91bef5aaf77457cb479433f948516bc https://www.frontiersin.org/article/10.3389/fmicb.2020.01844/full https://doaj.org/toc/1664-302X
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author2	Rosi Fassler Vaibhav Chikne Mor Goldenberg Tal Arian Liat Kolet Eliaz Oded Rimon Oren Ram Shulamit Michaeli Dana Reichmann
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up_date	2024-07-03T19:37:27.714Z
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