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Integrating Experiment and Theory to Understand TCR-pMHC Dynamics
The conformational dynamism of proteins is well established. Rather than having a single structure, proteins are more accurately described as a conformational ensemble that exists across a rugged energy landscape, where different conformational sub-states interconvert. The interaction between αβ T c...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293202/ https://www.ncbi.nlm.nih.gov/pubmed/30581442 http://dx.doi.org/10.3389/fimmu.2018.02898 |
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author | Buckle, Ashley M. Borg, Natalie A. |
author_facet | Buckle, Ashley M. Borg, Natalie A. |
author_sort | Buckle, Ashley M. |
collection | PubMed |
description | The conformational dynamism of proteins is well established. Rather than having a single structure, proteins are more accurately described as a conformational ensemble that exists across a rugged energy landscape, where different conformational sub-states interconvert. The interaction between αβ T cell receptors (TCR) and cognate peptide-MHC (pMHC) is no exception, and is a dynamic process that involves substantial conformational change. This review focuses on technological advances that have begun to establish the role of conformational dynamics and dynamic allostery in TCR recognition of the pMHC and the early stages of signaling. We discuss how the marriage of molecular dynamics (MD) simulations with experimental techniques provides us with new ways to dissect and interpret the process of TCR ligation. Notably, application of simulation techniques lags behind other fields, but is predicted to make substantial contributions. Finally, we highlight integrated approaches that are being used to shed light on some of the key outstanding questions in the early events leading to TCR signaling. |
format | Online Article Text |
id | pubmed-6293202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62932022018-12-21 Integrating Experiment and Theory to Understand TCR-pMHC Dynamics Buckle, Ashley M. Borg, Natalie A. Front Immunol Immunology The conformational dynamism of proteins is well established. Rather than having a single structure, proteins are more accurately described as a conformational ensemble that exists across a rugged energy landscape, where different conformational sub-states interconvert. The interaction between αβ T cell receptors (TCR) and cognate peptide-MHC (pMHC) is no exception, and is a dynamic process that involves substantial conformational change. This review focuses on technological advances that have begun to establish the role of conformational dynamics and dynamic allostery in TCR recognition of the pMHC and the early stages of signaling. We discuss how the marriage of molecular dynamics (MD) simulations with experimental techniques provides us with new ways to dissect and interpret the process of TCR ligation. Notably, application of simulation techniques lags behind other fields, but is predicted to make substantial contributions. Finally, we highlight integrated approaches that are being used to shed light on some of the key outstanding questions in the early events leading to TCR signaling. Frontiers Media S.A. 2018-12-07 /pmc/articles/PMC6293202/ /pubmed/30581442 http://dx.doi.org/10.3389/fimmu.2018.02898 Text en Copyright © 2018 Buckle and Borg. http://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 | Immunology Buckle, Ashley M. Borg, Natalie A. Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title | Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title_full | Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title_fullStr | Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title_full_unstemmed | Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title_short | Integrating Experiment and Theory to Understand TCR-pMHC Dynamics |
title_sort | integrating experiment and theory to understand tcr-pmhc dynamics |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293202/ https://www.ncbi.nlm.nih.gov/pubmed/30581442 http://dx.doi.org/10.3389/fimmu.2018.02898 |
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