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Retrieving functional pathways of biomolecules from single-particle snapshots
A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological condition...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501871/ https://www.ncbi.nlm.nih.gov/pubmed/32948759 http://dx.doi.org/10.1038/s41467-020-18403-x |
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author | Dashti, Ali Mashayekhi, Ghoncheh Shekhar, Mrinal Ben Hail, Danya Salah, Salah Schwander, Peter des Georges, Amedee Singharoy, Abhishek Frank, Joachim Ourmazd, Abbas |
author_facet | Dashti, Ali Mashayekhi, Ghoncheh Shekhar, Mrinal Ben Hail, Danya Salah, Salah Schwander, Peter des Georges, Amedee Singharoy, Abhishek Frank, Joachim Ourmazd, Abbas |
author_sort | Dashti, Ali |
collection | PubMed |
description | A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the binding of ligands. The functional motions differ substantially from those inferred from static structures in the nature of conformationally active structural domains, the sequence and extent of conformational motions, and the way allosteric signals are transduced within and between domains. Our approach highlights the importance of combining experiment, advanced data analysis, and molecular simulations. |
format | Online Article Text |
id | pubmed-7501871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75018712020-10-05 Retrieving functional pathways of biomolecules from single-particle snapshots Dashti, Ali Mashayekhi, Ghoncheh Shekhar, Mrinal Ben Hail, Danya Salah, Salah Schwander, Peter des Georges, Amedee Singharoy, Abhishek Frank, Joachim Ourmazd, Abbas Nat Commun Article A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the binding of ligands. The functional motions differ substantially from those inferred from static structures in the nature of conformationally active structural domains, the sequence and extent of conformational motions, and the way allosteric signals are transduced within and between domains. Our approach highlights the importance of combining experiment, advanced data analysis, and molecular simulations. Nature Publishing Group UK 2020-09-18 /pmc/articles/PMC7501871/ /pubmed/32948759 http://dx.doi.org/10.1038/s41467-020-18403-x Text en © The Author(s) 2020 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/. |
spellingShingle | Article Dashti, Ali Mashayekhi, Ghoncheh Shekhar, Mrinal Ben Hail, Danya Salah, Salah Schwander, Peter des Georges, Amedee Singharoy, Abhishek Frank, Joachim Ourmazd, Abbas Retrieving functional pathways of biomolecules from single-particle snapshots |
title | Retrieving functional pathways of biomolecules from single-particle snapshots |
title_full | Retrieving functional pathways of biomolecules from single-particle snapshots |
title_fullStr | Retrieving functional pathways of biomolecules from single-particle snapshots |
title_full_unstemmed | Retrieving functional pathways of biomolecules from single-particle snapshots |
title_short | Retrieving functional pathways of biomolecules from single-particle snapshots |
title_sort | retrieving functional pathways of biomolecules from single-particle snapshots |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501871/ https://www.ncbi.nlm.nih.gov/pubmed/32948759 http://dx.doi.org/10.1038/s41467-020-18403-x |
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