Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase

Autores
Morgada, Marcos Nicolás; Abriata, Luciano Andres; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; Vila, Alejandro Jose
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.
Fil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Abriata, Luciano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Cefaro, Chiara. Fondazione Farmacogenomica FiorGen Onlus; Italia
Fil: Gajda, Karolina. University of Florence; Italia
Fil: Banci, Lucia. Fondazione Farmacogenomica FiorGen Onlus; Italia. University of Florence; Italia
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Materia
CUA SITE
CYTOCHROME OXIDASE
METAL SITE ASSEMBLY
METALLOCHAPERONES
SCO PROTEINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45571
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/45571
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidaseMorgada, Marcos NicolásAbriata, Luciano AndresCefaro, ChiaraGajda, KarolinaBanci, LuciaVila, Alejandro JoseCUA SITECYTOCHROME OXIDASEMETAL SITE ASSEMBLYMETALLOCHAPERONESSCO PROTEINShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.Fil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Abriata, Luciano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Cefaro, Chiara. Fondazione Farmacogenomica FiorGen Onlus; ItaliaFil: Gajda, Karolina. University of Florence; ItaliaFil: Banci, Lucia. Fondazione Farmacogenomica FiorGen Onlus; Italia. University of Florence; ItaliaFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaNational Academy of Sciences2015-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45571Morgada, Marcos Nicolás; Abriata, Luciano Andres; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; et al.; Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 38; 9-2015; 11771-117760027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1505056112info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/38/11771info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:03:14Zoai:ri.conicet.gov.ar:11336/45571instacron: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:34982025-10-22 11:03:15.207CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
title Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
spellingShingle Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
Morgada, Marcos Nicolás
CUA SITE
CYTOCHROME OXIDASE
METAL SITE ASSEMBLY
METALLOCHAPERONES
SCO PROTEINS
title_short Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
title_full Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
title_fullStr Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
title_full_unstemmed Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
title_sort Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase
dc.creator.none.fl_str_mv Morgada, Marcos Nicolás
Abriata, Luciano Andres
Cefaro, Chiara
Gajda, Karolina
Banci, Lucia
Vila, Alejandro Jose
author Morgada, Marcos Nicolás
author_facet Morgada, Marcos Nicolás
Abriata, Luciano Andres
Cefaro, Chiara
Gajda, Karolina
Banci, Lucia
Vila, Alejandro Jose
author_role author
author2 Abriata, Luciano Andres
Cefaro, Chiara
Gajda, Karolina
Banci, Lucia
Vila, Alejandro Jose
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CUA SITE
CYTOCHROME OXIDASE
METAL SITE ASSEMBLY
METALLOCHAPERONES
SCO PROTEINS
topic CUA SITE
CYTOCHROME OXIDASE
METAL SITE ASSEMBLY
METALLOCHAPERONES
SCO PROTEINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.
Fil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Abriata, Luciano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Cefaro, Chiara. Fondazione Farmacogenomica FiorGen Onlus; Italia
Fil: Gajda, Karolina. University of Florence; Italia
Fil: Banci, Lucia. Fondazione Farmacogenomica FiorGen Onlus; Italia. University of Florence; Italia
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
description Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.
publishDate 2015
dc.date.none.fl_str_mv 2015-09
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/11336/45571
Morgada, Marcos Nicolás; Abriata, Luciano Andres; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; et al.; Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 38; 9-2015; 11771-11776
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45571
identifier_str_mv Morgada, Marcos Nicolás; Abriata, Luciano Andres; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; et al.; Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 38; 9-2015; 11771-11776
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1505056112
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/38/11771
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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
_version_ 1846781261078593536
score 12.982451

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