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Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6
Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, and the incorporation of essential cofactors. The human assembly factor Coa6 participates in the biogenesis of the Cu(A) site in complex IV (cytochrome c oxidase, COX). Pat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743065/ https://www.ncbi.nlm.nih.gov/pubmed/31515291 http://dx.doi.org/10.26508/lsa.201900458 |
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author | Maghool, Shadi Cooray, N Dinesha G Stroud, David A Aragão, David Ryan, Michael T Maher, Megan J |
author_facet | Maghool, Shadi Cooray, N Dinesha G Stroud, David A Aragão, David Ryan, Michael T Maher, Megan J |
author_sort | Maghool, Shadi |
collection | PubMed |
description | Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, and the incorporation of essential cofactors. The human assembly factor Coa6 participates in the biogenesis of the Cu(A) site in complex IV (cytochrome c oxidase, COX). Patients with mutations in Coa6 suffer from mitochondrial disease due to complex IV deficiency. Here, we present the crystal structures of human Coa6 and the pathogenic (W59C)Coa6-mutant protein. These structures show that Coa6 has a 3-helical bundle structure, with the first 2 helices tethered by disulfide bonds, one of which likely provides the copper-binding site. Disulfide-mediated oligomerization of the (W59C)Coa6 protein provides a structural explanation for the loss-of-function mutation. |
format | Online Article Text |
id | pubmed-6743065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-67430652019-09-27 Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 Maghool, Shadi Cooray, N Dinesha G Stroud, David A Aragão, David Ryan, Michael T Maher, Megan J Life Sci Alliance Research Articles Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, and the incorporation of essential cofactors. The human assembly factor Coa6 participates in the biogenesis of the Cu(A) site in complex IV (cytochrome c oxidase, COX). Patients with mutations in Coa6 suffer from mitochondrial disease due to complex IV deficiency. Here, we present the crystal structures of human Coa6 and the pathogenic (W59C)Coa6-mutant protein. These structures show that Coa6 has a 3-helical bundle structure, with the first 2 helices tethered by disulfide bonds, one of which likely provides the copper-binding site. Disulfide-mediated oligomerization of the (W59C)Coa6 protein provides a structural explanation for the loss-of-function mutation. Life Science Alliance LLC 2019-09-12 /pmc/articles/PMC6743065/ /pubmed/31515291 http://dx.doi.org/10.26508/lsa.201900458 Text en © 2019 Maghool et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Maghool, Shadi Cooray, N Dinesha G Stroud, David A Aragão, David Ryan, Michael T Maher, Megan J Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title | Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title_full | Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title_fullStr | Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title_full_unstemmed | Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title_short | Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 |
title_sort | structural and functional characterization of the mitochondrial complex iv assembly factor coa6 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743065/ https://www.ncbi.nlm.nih.gov/pubmed/31515291 http://dx.doi.org/10.26508/lsa.201900458 |
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