Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus

Autores
Doni, Davide; Cavallari, Eva; Noguera, Martín Ezequiel; Gentili, Hernan Gustavo; Cavion, Federica; Parisi, Gustavo Daniel; Fornasari, Maria Silvina; Sartori, Geppo; Santos, Javier; Bellanda, Massimo; Carbonera, Donatella; Costantini, Paola; Bortolus, Marco
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, withstrong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial diseaseFriedreich’s ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 canameliorate the respiratory phenotype of FRDA patients’ cells, and this prompted us to furthercharacterize both the Nqo15 solution’s behavior and its potential functional overlap with FXN, usinga combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN byperforming extensive database searches based on sequence and structure. Nqo15’s folding andflexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism,and coarse-grained molecular dynamics simulations. Nqo15’s iron-binding properties were studiedusing NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. Wefound that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution,and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfuraseactivation function.
Fil: Doni, Davide. Università di Padova; Italia
Fil: Cavallari, Eva. Università di Padova; Italia
Fil: Noguera, Martín Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gentili, Hernan Gustavo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cavion, Federica. Università di Padova; Italia
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Sartori, Geppo. Università di Padova; Italia
Fil: Santos, Javier. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Bellanda, Massimo. Università di Padova; Italia
Fil: Carbonera, Donatella. Università di Padova; Italia
Fil: Costantini, Paola. Università di Padova; Italia
Fil: Bortolus, Marco. Università di Padova; Italia
Materia
NqO15
frataxin
Friedreich Ataxia
Thermus thermophilus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/231759
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/231759
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilusDoni, DavideCavallari, EvaNoguera, Martín EzequielGentili, Hernan GustavoCavion, FedericaParisi, Gustavo DanielFornasari, Maria SilvinaSartori, GeppoSantos, JavierBellanda, MassimoCarbonera, DonatellaCostantini, PaolaBortolus, MarcoNqO15frataxinFriedreich AtaxiaThermus thermophilushttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, withstrong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial diseaseFriedreich’s ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 canameliorate the respiratory phenotype of FRDA patients’ cells, and this prompted us to furthercharacterize both the Nqo15 solution’s behavior and its potential functional overlap with FXN, usinga combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN byperforming extensive database searches based on sequence and structure. Nqo15’s folding andflexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism,and coarse-grained molecular dynamics simulations. Nqo15’s iron-binding properties were studiedusing NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. Wefound that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution,and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfuraseactivation function.Fil: Doni, Davide. Università di Padova; ItaliaFil: Cavallari, Eva. Università di Padova; ItaliaFil: Noguera, Martín Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Gentili, Hernan Gustavo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cavion, Federica. Università di Padova; ItaliaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Sartori, Geppo. Università di Padova; ItaliaFil: Santos, Javier. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaFil: Bellanda, Massimo. Università di Padova; ItaliaFil: Carbonera, Donatella. Università di Padova; ItaliaFil: Costantini, Paola. Università di Padova; ItaliaFil: Bortolus, Marco. Università di Padova; ItaliaMolecular Diversity Preservation International2024-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/231759Doni, Davide; Cavallari, Eva; Noguera, Martín Ezequiel; Gentili, Hernan Gustavo; Cavion, Federica; et al.; Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 3; 2-2024; 1-181422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/25/3/1912info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms25031912info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:47Zoai:ri.conicet.gov.ar:11336/231759instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:54:47.388CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
title Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
spellingShingle Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
Doni, Davide
NqO15
frataxin
Friedreich Ataxia
Thermus thermophilus
title_short Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
title_full Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
title_fullStr Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
title_full_unstemmed Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
title_sort Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
dc.creator.none.fl_str_mv Doni, Davide
Cavallari, Eva
Noguera, Martín Ezequiel
Gentili, Hernan Gustavo
Cavion, Federica
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Sartori, Geppo
Santos, Javier
Bellanda, Massimo
Carbonera, Donatella
Costantini, Paola
Bortolus, Marco
author Doni, Davide
author_facet Doni, Davide
Cavallari, Eva
Noguera, Martín Ezequiel
Gentili, Hernan Gustavo
Cavion, Federica
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Sartori, Geppo
Santos, Javier
Bellanda, Massimo
Carbonera, Donatella
Costantini, Paola
Bortolus, Marco
author_role author
author2 Cavallari, Eva
Noguera, Martín Ezequiel
Gentili, Hernan Gustavo
Cavion, Federica
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Sartori, Geppo
Santos, Javier
Bellanda, Massimo
Carbonera, Donatella
Costantini, Paola
Bortolus, Marco
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NqO15
frataxin
Friedreich Ataxia
Thermus thermophilus
topic NqO15
frataxin
Friedreich Ataxia
Thermus thermophilus
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, withstrong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial diseaseFriedreich’s ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 canameliorate the respiratory phenotype of FRDA patients’ cells, and this prompted us to furthercharacterize both the Nqo15 solution’s behavior and its potential functional overlap with FXN, usinga combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN byperforming extensive database searches based on sequence and structure. Nqo15’s folding andflexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism,and coarse-grained molecular dynamics simulations. Nqo15’s iron-binding properties were studiedusing NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. Wefound that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution,and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfuraseactivation function.
Fil: Doni, Davide. Università di Padova; Italia
Fil: Cavallari, Eva. Università di Padova; Italia
Fil: Noguera, Martín Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gentili, Hernan Gustavo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cavion, Federica. Università di Padova; Italia
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Sartori, Geppo. Università di Padova; Italia
Fil: Santos, Javier. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Bellanda, Massimo. Università di Padova; Italia
Fil: Carbonera, Donatella. Università di Padova; Italia
Fil: Costantini, Paola. Università di Padova; Italia
Fil: Bortolus, Marco. Università di Padova; Italia
description Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, withstrong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial diseaseFriedreich’s ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 canameliorate the respiratory phenotype of FRDA patients’ cells, and this prompted us to furthercharacterize both the Nqo15 solution’s behavior and its potential functional overlap with FXN, usinga combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN byperforming extensive database searches based on sequence and structure. Nqo15’s folding andflexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism,and coarse-grained molecular dynamics simulations. Nqo15’s iron-binding properties were studiedusing NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. Wefound that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution,and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfuraseactivation function.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/231759
Doni, Davide; Cavallari, Eva; Noguera, Martín Ezequiel; Gentili, Hernan Gustavo; Cavion, Federica; et al.; Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 3; 2-2024; 1-18
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/231759
identifier_str_mv Doni, Davide; Cavallari, Eva; Noguera, Martín Ezequiel; Gentili, Hernan Gustavo; Cavion, Federica; et al.; Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 3; 2-2024; 1-18
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/25/3/1912
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms25031912
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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