COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase

In eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones a...

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Autores principales:	Soma, Shivatheja, Morgada, Marcos Nicolás, Naik, Mandar T., Boulet, Aren, Roesler, Anna A., Dziuba, Nathaniel, Ghosh, Alok, Yu, Qinhong, Lindahl, Paul A., Ames, James B., Leary, Scot C., Vila, Alejandro J., Gohil, Vishal M.
Formato:	article artículo publishedVersion
Lenguaje:	Inglés
Publicado:	Cell Press 2021
Materias:	Cytochrome c Oxidase Assembly factor 6 (COA6) Cytochrome c Oxidase subunit 2 (COX2) Mitochondria SCO1 Cytochrome c Oxidase Assembly Protein 1 SCO2 Cytochrome c Oxidase Assembly Protein 2 Copper Metallochaperones
Acceso en línea:	http://hdl.handle.net/2133/19986 http://hdl.handle.net/2133/19986
Aporte de:	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario

id	I15-R121-2133-19986
record_format	dspace
institution	Universidad Nacional de Rosario
institution_str	I-15
repository_str	R-121
collection	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language	Inglés
topic	Cytochrome c Oxidase Assembly factor 6 (COA6) Cytochrome c Oxidase subunit 2 (COX2) Mitochondria SCO1 Cytochrome c Oxidase Assembly Protein 1 SCO2 Cytochrome c Oxidase Assembly Protein 2 Copper Metallochaperones
spellingShingle	Cytochrome c Oxidase Assembly factor 6 (COA6) Cytochrome c Oxidase subunit 2 (COX2) Mitochondria SCO1 Cytochrome c Oxidase Assembly Protein 1 SCO2 Cytochrome c Oxidase Assembly Protein 2 Copper Metallochaperones Soma, Shivatheja Morgada, Marcos Nicolás Naik, Mandar T. Boulet, Aren Roesler, Anna A. Dziuba, Nathaniel Ghosh, Alok Yu, Qinhong Lindahl, Paul A. Ames, James B. Leary, Scot C. Vila, Alejandro J. Gohil, Vishal M. COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
topic_facet	Cytochrome c Oxidase Assembly factor 6 (COA6) Cytochrome c Oxidase subunit 2 (COX2) Mitochondria SCO1 Cytochrome c Oxidase Assembly Protein 1 SCO2 Cytochrome c Oxidase Assembly Protein 2 Copper Metallochaperones
description	In eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6, a recently discovered protein whose molecular function is unknown. To uncover the molecular mechanism by which COA6 and SCO proteins mediate copper delivery to COX2, we have solved the solution structure of COA6, which reveals a coiled-coil-helix-coiled-coilhelix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. Accordingly, we demonstrate that COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Finally, our determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO.
format	article artículo publishedVersion
author	Soma, Shivatheja Morgada, Marcos Nicolás Naik, Mandar T. Boulet, Aren Roesler, Anna A. Dziuba, Nathaniel Ghosh, Alok Yu, Qinhong Lindahl, Paul A. Ames, James B. Leary, Scot C. Vila, Alejandro J. Gohil, Vishal M.
author_facet	Soma, Shivatheja Morgada, Marcos Nicolás Naik, Mandar T. Boulet, Aren Roesler, Anna A. Dziuba, Nathaniel Ghosh, Alok Yu, Qinhong Lindahl, Paul A. Ames, James B. Leary, Scot C. Vila, Alejandro J. Gohil, Vishal M.
author_sort	Soma, Shivatheja
title	COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
title_short	COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
title_full	COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
title_fullStr	COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
title_full_unstemmed	COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
title_sort	coa6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase
publisher	Cell Press
publishDate	2021
url	http://hdl.handle.net/2133/19986 http://hdl.handle.net/2133/19986
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bdutipo_str	Repositorios
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COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase

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