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 C_ 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.
All 6000 molecular dynamics structures of the membrane-embedded TCR-CD3 complex used in the analysis have been deposited in the Edmond Open Research Data Repository under https://dx.doi.org/10.17617/3.5m.
MD simulation structures of the membrane-embedded TCR - CD3 complexEdmond Open Research Data Repository of the Max Planck Society.
The authors declare that there was no funding for this work.
- Michael L Dustin, University of Oxford, United Kingdom
- Received: February 3, 2021
- Accepted: September 6, 2021
- Accepted Manuscript published: September 7, 2021 (version 1)
© 2021, Pandey et al.
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