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The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin

BACKGROUND: The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. RESULTS: We found that in amniotes HAP40 is encoded by a single-e...

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Autores principales: Seefelder, Manuel, Alva, Vikram, Huang, Bin, Engler, Tatjana, Baumeister, Wolfgang, Guo, Qiang, Fernández-Busnadiego, Rubén, Lupas, Andrei N., Kochanek, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725122/
https://www.ncbi.nlm.nih.gov/pubmed/33297953
http://dx.doi.org/10.1186/s12862-020-01705-5
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author Seefelder, Manuel
Alva, Vikram
Huang, Bin
Engler, Tatjana
Baumeister, Wolfgang
Guo, Qiang
Fernández-Busnadiego, Rubén
Lupas, Andrei N.
Kochanek, Stefan
author_facet Seefelder, Manuel
Alva, Vikram
Huang, Bin
Engler, Tatjana
Baumeister, Wolfgang
Guo, Qiang
Fernández-Busnadiego, Rubén
Lupas, Andrei N.
Kochanek, Stefan
author_sort Seefelder, Manuel
collection PubMed
description BACKGROUND: The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. RESULTS: We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs). CONCLUSION: Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.
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spelling pubmed-77251222020-12-10 The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin Seefelder, Manuel Alva, Vikram Huang, Bin Engler, Tatjana Baumeister, Wolfgang Guo, Qiang Fernández-Busnadiego, Rubén Lupas, Andrei N. Kochanek, Stefan BMC Evol Biol Research Article BACKGROUND: The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. RESULTS: We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs). CONCLUSION: Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction. BioMed Central 2020-12-09 /pmc/articles/PMC7725122/ /pubmed/33297953 http://dx.doi.org/10.1186/s12862-020-01705-5 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Seefelder, Manuel
Alva, Vikram
Huang, Bin
Engler, Tatjana
Baumeister, Wolfgang
Guo, Qiang
Fernández-Busnadiego, Rubén
Lupas, Andrei N.
Kochanek, Stefan
The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title_full The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title_fullStr The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title_full_unstemmed The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title_short The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
title_sort evolution of the huntingtin-associated protein 40 (hap40) in conjunction with huntingtin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725122/
https://www.ncbi.nlm.nih.gov/pubmed/33297953
http://dx.doi.org/10.1186/s12862-020-01705-5
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