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Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β
Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296144/ https://www.ncbi.nlm.nih.gov/pubmed/34307465 http://dx.doi.org/10.3389/fmolb.2021.716477 |
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author | Dubrow, Alyssa Kim, Iktae Topo, Elias Cho, Jae-Hyun |
author_facet | Dubrow, Alyssa Kim, Iktae Topo, Elias Cho, Jae-Hyun |
author_sort | Dubrow, Alyssa |
collection | PubMed |
description | Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic resolution. However, to fully understand the role of the conformational dynamics in molecular recognition, studies on the binding transition state are needed. Here, we investigate the binding transition state between nonstructural protein 1 (NS1) of the pandemic 1918 influenza A virus and the human p85β subunit of PI3K. 1918 NS1 binds to p85β via conformational selection. We present the free-energy mapping of the transition and bound states of the 1918 NS1:p85β interaction using linear free energy relationship and ϕ-value analyses. We find that the binding transition state of 1918 NS1 and p85β is structurally similar to the bound state with well-defined binding orientation and hydrophobic interactions. Our finding provides a detailed view of how protein motion contributes to the development of intermolecular interactions along the binding reaction coordinate. |
format | Online Article Text |
id | pubmed-8296144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82961442021-07-23 Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β Dubrow, Alyssa Kim, Iktae Topo, Elias Cho, Jae-Hyun Front Mol Biosci Molecular Biosciences Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic resolution. However, to fully understand the role of the conformational dynamics in molecular recognition, studies on the binding transition state are needed. Here, we investigate the binding transition state between nonstructural protein 1 (NS1) of the pandemic 1918 influenza A virus and the human p85β subunit of PI3K. 1918 NS1 binds to p85β via conformational selection. We present the free-energy mapping of the transition and bound states of the 1918 NS1:p85β interaction using linear free energy relationship and ϕ-value analyses. We find that the binding transition state of 1918 NS1 and p85β is structurally similar to the bound state with well-defined binding orientation and hydrophobic interactions. Our finding provides a detailed view of how protein motion contributes to the development of intermolecular interactions along the binding reaction coordinate. Frontiers Media S.A. 2021-07-08 /pmc/articles/PMC8296144/ /pubmed/34307465 http://dx.doi.org/10.3389/fmolb.2021.716477 Text en Copyright © 2021 Dubrow, Kim, Topo and Cho. 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 Dubrow, Alyssa Kim, Iktae Topo, Elias Cho, Jae-Hyun Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title | Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title_full | Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title_fullStr | Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title_full_unstemmed | Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title_short | Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β |
title_sort | understanding the binding transition state after the conformational selection step: the second half of the molecular recognition process between ns1 of the 1918 influenza virus and host p85β |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296144/ https://www.ncbi.nlm.nih.gov/pubmed/34307465 http://dx.doi.org/10.3389/fmolb.2021.716477 |
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