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Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations
Allostery is usually considered to be a mechanism for transmission of signals associated with physical or dynamic changes in some part of a protein. Here, we investigate the changes in fluctuations across the protein upon ligand binding based on the fluctuations computed with elastic network models....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440829/ https://www.ncbi.nlm.nih.gov/pubmed/34540902 http://dx.doi.org/10.3389/fmolb.2021.733148 |
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author | Kumar, Ambuj Jernigan, Robert L. |
author_facet | Kumar, Ambuj Jernigan, Robert L. |
author_sort | Kumar, Ambuj |
collection | PubMed |
description | Allostery is usually considered to be a mechanism for transmission of signals associated with physical or dynamic changes in some part of a protein. Here, we investigate the changes in fluctuations across the protein upon ligand binding based on the fluctuations computed with elastic network models. These results suggest that binding reduces the fluctuations at the binding site but increases fluctuations at remote sites, but not to fully compensating extents. If there were complete conservation of entropy, then only the enthalpies of binding would matter and not the entropies; however this does not appear to be the case. Experimental evidence also suggests that energies and entropies of binding can compensate but that the extent of compensation varies widely from case to case. Our results do however always show transmission of an allosteric signal to distant locations where the fluctuations are increased. These fluctuations could be used to compute entropies to improve evaluations of the thermodynamics of binding. We also show the allosteric relationship between peptide binding in the GroEL trans-ring that leads directly to the release of GroES from the GroEL-GroES cis-ring. This finding provides an example of how calculating these changes to protein dynamics induced by the binding of an allosteric ligand can regulate protein function and mechanism. |
format | Online Article Text |
id | pubmed-8440829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84408292021-09-16 Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations Kumar, Ambuj Jernigan, Robert L. Front Mol Biosci Molecular Biosciences Allostery is usually considered to be a mechanism for transmission of signals associated with physical or dynamic changes in some part of a protein. Here, we investigate the changes in fluctuations across the protein upon ligand binding based on the fluctuations computed with elastic network models. These results suggest that binding reduces the fluctuations at the binding site but increases fluctuations at remote sites, but not to fully compensating extents. If there were complete conservation of entropy, then only the enthalpies of binding would matter and not the entropies; however this does not appear to be the case. Experimental evidence also suggests that energies and entropies of binding can compensate but that the extent of compensation varies widely from case to case. Our results do however always show transmission of an allosteric signal to distant locations where the fluctuations are increased. These fluctuations could be used to compute entropies to improve evaluations of the thermodynamics of binding. We also show the allosteric relationship between peptide binding in the GroEL trans-ring that leads directly to the release of GroES from the GroEL-GroES cis-ring. This finding provides an example of how calculating these changes to protein dynamics induced by the binding of an allosteric ligand can regulate protein function and mechanism. Frontiers Media S.A. 2021-09-01 /pmc/articles/PMC8440829/ /pubmed/34540902 http://dx.doi.org/10.3389/fmolb.2021.733148 Text en Copyright © 2021 Kumar and Jernigan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Kumar, Ambuj Jernigan, Robert L. Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title | Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title_full | Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title_fullStr | Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title_full_unstemmed | Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title_short | Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations |
title_sort | ligand binding introduces significant allosteric shifts in the locations of protein fluctuations |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440829/ https://www.ncbi.nlm.nih.gov/pubmed/34540902 http://dx.doi.org/10.3389/fmolb.2021.733148 |
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