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The structure and evolutionary diversity of the fungal E3-binding protein

The pyruvate dehydrogenase complex (PDC) is a central metabolic enzyme in all living cells composed majorly of E1, E2, and E3. Tight coupling of their reactions makes each component essential, so that any loss impacts oxidative metabolism pathologically. E3 retention is mediated by the E3-binding pr...

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Autor principal: Forsberg, Bjoern O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156792/
https://www.ncbi.nlm.nih.gov/pubmed/37137945
http://dx.doi.org/10.1038/s42003-023-04854-7
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author Forsberg, Bjoern O.
author_facet Forsberg, Bjoern O.
author_sort Forsberg, Bjoern O.
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description The pyruvate dehydrogenase complex (PDC) is a central metabolic enzyme in all living cells composed majorly of E1, E2, and E3. Tight coupling of their reactions makes each component essential, so that any loss impacts oxidative metabolism pathologically. E3 retention is mediated by the E3-binding protein (E3BP), which is here resolved within the PDC core from N.crassa, resolved to 3.2Å. Fungal and mammalian E3BP are shown to be orthologs, arguing E3BP as a broadly eukaryotic gene. Fungal E3BP architectures predicted from sequence data and computational models further bridge the evolutionary distance between N.crassa and humans, and suggest discriminants for E3-specificity. This is confirmed by similarities in their respective E3-binding domains, where an interaction previously not described is also predicted. This provides evolutionary parallels for a crucial interaction human metabolism, an interaction specific to fungi that can be targeted, and an example of protein evolution following gene neofunctionalization.
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spelling pubmed-101567922023-05-05 The structure and evolutionary diversity of the fungal E3-binding protein Forsberg, Bjoern O. Commun Biol Article The pyruvate dehydrogenase complex (PDC) is a central metabolic enzyme in all living cells composed majorly of E1, E2, and E3. Tight coupling of their reactions makes each component essential, so that any loss impacts oxidative metabolism pathologically. E3 retention is mediated by the E3-binding protein (E3BP), which is here resolved within the PDC core from N.crassa, resolved to 3.2Å. Fungal and mammalian E3BP are shown to be orthologs, arguing E3BP as a broadly eukaryotic gene. Fungal E3BP architectures predicted from sequence data and computational models further bridge the evolutionary distance between N.crassa and humans, and suggest discriminants for E3-specificity. This is confirmed by similarities in their respective E3-binding domains, where an interaction previously not described is also predicted. This provides evolutionary parallels for a crucial interaction human metabolism, an interaction specific to fungi that can be targeted, and an example of protein evolution following gene neofunctionalization. Nature Publishing Group UK 2023-05-03 /pmc/articles/PMC10156792/ /pubmed/37137945 http://dx.doi.org/10.1038/s42003-023-04854-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Forsberg, Bjoern O.
The structure and evolutionary diversity of the fungal E3-binding protein
title The structure and evolutionary diversity of the fungal E3-binding protein
title_full The structure and evolutionary diversity of the fungal E3-binding protein
title_fullStr The structure and evolutionary diversity of the fungal E3-binding protein
title_full_unstemmed The structure and evolutionary diversity of the fungal E3-binding protein
title_short The structure and evolutionary diversity of the fungal E3-binding protein
title_sort structure and evolutionary diversity of the fungal e3-binding protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156792/
https://www.ncbi.nlm.nih.gov/pubmed/37137945
http://dx.doi.org/10.1038/s42003-023-04854-7
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