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Amyloid-Associated Nucleic Acid Hybridisation
Nucleic acids promote amyloid formation in diseases including Alzheimer's and Creutzfeldt-Jakob disease. However, it remains unclear whether the close interactions between amyloid and nucleic acid allow nucleic acid secondary structure to play a role in modulating amyloid structure and function...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098241/ https://www.ncbi.nlm.nih.gov/pubmed/21625537 http://dx.doi.org/10.1371/journal.pone.0019125 |
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author | Braun, Sebastian Humphreys, Christine Fraser, Elizabeth Brancale, Andrea Bochtler, Matthias Dale, Trevor C. |
author_facet | Braun, Sebastian Humphreys, Christine Fraser, Elizabeth Brancale, Andrea Bochtler, Matthias Dale, Trevor C. |
author_sort | Braun, Sebastian |
collection | PubMed |
description | Nucleic acids promote amyloid formation in diseases including Alzheimer's and Creutzfeldt-Jakob disease. However, it remains unclear whether the close interactions between amyloid and nucleic acid allow nucleic acid secondary structure to play a role in modulating amyloid structure and function. Here we have used a simplified system of short basic peptides with alternating hydrophobic and hydrophilic amino acid residues to study nucleic acid - amyloid interactions. Employing biophysical techniques including X-ray fibre diffraction, circular dichroism spectroscopy and electron microscopy we show that the polymerized charges of nucleic acids concentrate and enhance the formation of amyloid from short basic peptides, many of which would not otherwise form fibres. In turn, the amyloid component binds nucleic acids and promotes their hybridisation at concentrations below their solution K (d), as shown by time-resolved FRET studies. The self-reinforcing interactions between peptides and nucleic acids lead to the formation of amyloid nucleic acid (ANA) fibres whose properties are distinct from their component polymers. In addition to their importance in disease and potential in engineering, ANA fibres formed from prebiotically-produced peptides and nucleic acids may have played a role in early evolution, constituting the first entities subject to Darwinian evolution. |
format | Text |
id | pubmed-3098241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30982412011-05-27 Amyloid-Associated Nucleic Acid Hybridisation Braun, Sebastian Humphreys, Christine Fraser, Elizabeth Brancale, Andrea Bochtler, Matthias Dale, Trevor C. PLoS One Research Article Nucleic acids promote amyloid formation in diseases including Alzheimer's and Creutzfeldt-Jakob disease. However, it remains unclear whether the close interactions between amyloid and nucleic acid allow nucleic acid secondary structure to play a role in modulating amyloid structure and function. Here we have used a simplified system of short basic peptides with alternating hydrophobic and hydrophilic amino acid residues to study nucleic acid - amyloid interactions. Employing biophysical techniques including X-ray fibre diffraction, circular dichroism spectroscopy and electron microscopy we show that the polymerized charges of nucleic acids concentrate and enhance the formation of amyloid from short basic peptides, many of which would not otherwise form fibres. In turn, the amyloid component binds nucleic acids and promotes their hybridisation at concentrations below their solution K (d), as shown by time-resolved FRET studies. The self-reinforcing interactions between peptides and nucleic acids lead to the formation of amyloid nucleic acid (ANA) fibres whose properties are distinct from their component polymers. In addition to their importance in disease and potential in engineering, ANA fibres formed from prebiotically-produced peptides and nucleic acids may have played a role in early evolution, constituting the first entities subject to Darwinian evolution. Public Library of Science 2011-05-19 /pmc/articles/PMC3098241/ /pubmed/21625537 http://dx.doi.org/10.1371/journal.pone.0019125 Text en Braun et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Braun, Sebastian Humphreys, Christine Fraser, Elizabeth Brancale, Andrea Bochtler, Matthias Dale, Trevor C. Amyloid-Associated Nucleic Acid Hybridisation |
title | Amyloid-Associated Nucleic Acid Hybridisation |
title_full | Amyloid-Associated Nucleic Acid Hybridisation |
title_fullStr | Amyloid-Associated Nucleic Acid Hybridisation |
title_full_unstemmed | Amyloid-Associated Nucleic Acid Hybridisation |
title_short | Amyloid-Associated Nucleic Acid Hybridisation |
title_sort | amyloid-associated nucleic acid hybridisation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098241/ https://www.ncbi.nlm.nih.gov/pubmed/21625537 http://dx.doi.org/10.1371/journal.pone.0019125 |
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