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Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP
Given the emergence of the severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which particularly threatens older people with comorbidities such as diabetes mellitus and dementia, understanding the relationship between Covid‐19 and other diseases is an important factor for treatment. Possi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015630/ https://www.ncbi.nlm.nih.gov/pubmed/34882862 http://dx.doi.org/10.1002/chem.202104182 |
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author | Mukherjee, Sanjib K. Knop, Jim‐Marcel Winter, Roland |
author_facet | Mukherjee, Sanjib K. Knop, Jim‐Marcel Winter, Roland |
author_sort | Mukherjee, Sanjib K. |
collection | PubMed |
description | Given the emergence of the severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which particularly threatens older people with comorbidities such as diabetes mellitus and dementia, understanding the relationship between Covid‐19 and other diseases is an important factor for treatment. Possible targets for medical intervention include G‐quadruplexes (G4Qs) and their protein interaction partners. We investigated the stability and conformational space of the RG‐1 RNA‐G‐quadruplex of the SARS‐CoV‐2 N‐gene in the presence of salts, cosolutes, crowders and intrinsically disordered peptides, focusing on α‐Synuclein and the human islet amyloid polypeptide, which are involved in Parkinson's disease (PD) and type‐II diabetes mellitus (T2DM), respectively. We found that the conformational dynamics of the RG‐1 G4Q is strongly affected by the various solution conditions. Further, the amyloidogenic peptides were found to strongly modulate the conformational equilibrium of the RG‐1. Considerable changes are observed with respect to their interaction with human telomeric G4Qs, which adopt different topologies. These results may therefore shed more light on the relationship between PD as well as T2DM and the SARS‐CoV‐2 disease and their molecular underpinnings. Since dysregulation of G4Q formation by rationally designed targeting compounds affects the control of cellular processes, this study should contribute to the development of specific ligands for intervention. |
format | Online Article Text |
id | pubmed-9015630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90156302022-04-19 Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP Mukherjee, Sanjib K. Knop, Jim‐Marcel Winter, Roland Chemistry Research Articles Given the emergence of the severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which particularly threatens older people with comorbidities such as diabetes mellitus and dementia, understanding the relationship between Covid‐19 and other diseases is an important factor for treatment. Possible targets for medical intervention include G‐quadruplexes (G4Qs) and their protein interaction partners. We investigated the stability and conformational space of the RG‐1 RNA‐G‐quadruplex of the SARS‐CoV‐2 N‐gene in the presence of salts, cosolutes, crowders and intrinsically disordered peptides, focusing on α‐Synuclein and the human islet amyloid polypeptide, which are involved in Parkinson's disease (PD) and type‐II diabetes mellitus (T2DM), respectively. We found that the conformational dynamics of the RG‐1 G4Q is strongly affected by the various solution conditions. Further, the amyloidogenic peptides were found to strongly modulate the conformational equilibrium of the RG‐1. Considerable changes are observed with respect to their interaction with human telomeric G4Qs, which adopt different topologies. These results may therefore shed more light on the relationship between PD as well as T2DM and the SARS‐CoV‐2 disease and their molecular underpinnings. Since dysregulation of G4Q formation by rationally designed targeting compounds affects the control of cellular processes, this study should contribute to the development of specific ligands for intervention. John Wiley and Sons Inc. 2022-01-05 2022-02-16 /pmc/articles/PMC9015630/ /pubmed/34882862 http://dx.doi.org/10.1002/chem.202104182 Text en © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Mukherjee, Sanjib K. Knop, Jim‐Marcel Winter, Roland Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title | Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title_full | Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title_fullStr | Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title_full_unstemmed | Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title_short | Modulation of the Conformational Space of SARS‐CoV‐2 RNA Quadruplex RG‐1 by Cellular Components and the Amyloidogenic Peptides α‐Synuclein and hIAPP |
title_sort | modulation of the conformational space of sars‐cov‐2 rna quadruplex rg‐1 by cellular components and the amyloidogenic peptides α‐synuclein and hiapp |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015630/ https://www.ncbi.nlm.nih.gov/pubmed/34882862 http://dx.doi.org/10.1002/chem.202104182 |
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