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Structural variability and concerted motions of the T cell receptor – CD3 complex
We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) – CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al., 2019. We find that the TCR extracellular (EC) domain is high...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504971/ https://www.ncbi.nlm.nih.gov/pubmed/34490842 http://dx.doi.org/10.7554/eLife.67195 |
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author | Pandey, Prithvi R Różycki, Bartosz Lipowsky, Reinhard Weikl, Thomas R |
author_facet | Pandey, Prithvi R Różycki, Bartosz Lipowsky, Reinhard Weikl, Thomas R |
author_sort | Pandey, Prithvi R |
collection | PubMed |
description | We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) – CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al., 2019. We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR – CD3 complex, in particular in the EC interactions of the Cβ FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR – CD3 complex revealed in our simulations provide atomistic insights on conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs. |
format | Online Article Text |
id | pubmed-8504971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85049712021-10-13 Structural variability and concerted motions of the T cell receptor – CD3 complex Pandey, Prithvi R Różycki, Bartosz Lipowsky, Reinhard Weikl, Thomas R eLife Immunology and Inflammation We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) – CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al., 2019. We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR – CD3 complex, in particular in the EC interactions of the Cβ FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR – CD3 complex revealed in our simulations provide atomistic insights on conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs. eLife Sciences Publications, Ltd 2021-09-07 /pmc/articles/PMC8504971/ /pubmed/34490842 http://dx.doi.org/10.7554/eLife.67195 Text en © 2021, Pandey et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Pandey, Prithvi R Różycki, Bartosz Lipowsky, Reinhard Weikl, Thomas R Structural variability and concerted motions of the T cell receptor – CD3 complex |
title | Structural variability and concerted motions of the T cell receptor – CD3 complex |
title_full | Structural variability and concerted motions of the T cell receptor – CD3 complex |
title_fullStr | Structural variability and concerted motions of the T cell receptor – CD3 complex |
title_full_unstemmed | Structural variability and concerted motions of the T cell receptor – CD3 complex |
title_short | Structural variability and concerted motions of the T cell receptor – CD3 complex |
title_sort | structural variability and concerted motions of the t cell receptor – cd3 complex |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504971/ https://www.ncbi.nlm.nih.gov/pubmed/34490842 http://dx.doi.org/10.7554/eLife.67195 |
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