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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/45571
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:35:13Zoai: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:34982025-09-29 09:35:13.387CONICET 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 |
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1844613095340638208 |
score |
13.070432 |