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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...

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Autores principales: Pandey, Prithvi R, Różycki, Bartosz, Lipowsky, Reinhard, Weikl, Thomas R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
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.
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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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