Experimentally guided computational methods yield highly accurate insights into transmembrane interactions within the T cell receptor complex
Journal Title
Journal of Physical Chemistry B
Publication Type
Journal epub ahead of print
Abstract
Understanding how molecular interactions within the plasma membrane govern assembly, clustering, and conformational changes in single-pass transmembrane (TM) receptors has long presented substantial experimental challenges. Our previous work on activating immune receptors has combined direct biochemical and biophysical characterizations with both independent and experimentally restrained computational methods to provide novel insights into the key TM interactions underpinning assembly and stability of complex, multisubunit receptor systems. The recently published cryo-EM structure of the intact T cell receptor (TCR)-CD3 complex provides a unique opportunity to test the models and predictions arising from these studies, and we find that they are accurate, which we attribute to robust simulation environments and careful consideration of limitations related to studying TM interactions in isolation from additional receptor domains. With this in mind, we revisit results in other immune receptors and look forward to how similar methods may be applied to understand receptors for which little or no structural information is currently available.
Publisher
ACS
Research Division(s)
Structural Biology
PubMed ID
33030343
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-11-02 04:55:18
Last Modified: 2020-11-03 09:24:49
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