Experimentally Guided Computational Methods Yield Highly Accurate Insights into Transmembrane Interactions within the T Cell Receptor Complex
| Autor: | Soohyung Park, Matthew E. Call, Wonpil Im, Samyuktha Ramesh, Melissa J. Call |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Molecular interactions
T cell receptor complex 010304 chemical physics Protein Conformation Cell Membrane T-cell receptor Computational biology 010402 general chemistry 01 natural sciences Transmembrane protein 0104 chemical sciences Surfaces Coatings and Films Receptor-CD3 Complex Antigen T-Cell 0103 physical sciences Materials Chemistry Humans Physical and Theoretical Chemistry Receptor |
| Zdroj: | The Journal of Physical Chemistry B. 124:10303-10310 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.0c06403 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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