Experimentally Guided Computational Methods Yield Highly Accurate Insights into Transmembrane Interactions within the T Cell Receptor Complex,The Journal of Physical Chemistry B

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Experimentally Guided Computational Methods Yield Highly Accurate Insights into Transmembrane Interactions within the T Cell Receptor Complex
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2020-10-08 , DOI: 10.1021/acs.jpcb.0c06403
Samyuktha Ramesh _{1,

2} , Soohyung Park ₃ , Melissa J Call _{1,

2} , Wonpil Im ₃ , Matthew E Call _{1,

2}

Affiliation

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.

中文翻译：

实验指导的计算方法对 T 细胞受体复合物中的跨膜相互作用产生了高度准确的见解

了解质膜内的分子相互作用如何控制单次跨膜 (TM) 受体的组装、聚集和构象变化，长期以来一直存在重大的实验挑战。我们之前在激活免疫受体方面的工作将直接的生化和生物物理表征与独立和实验受限的计算方法相结合，为支持复杂多亚基受体系统的组装和稳定性的关键 TM 相互作用提供了新的见解。最近发表的完整 T 细胞受体 (TCR)-CD3 复合物的冷冻电镜结构为测试这些研究产生的模型和预测提供了独特的机会，我们发现它们是准确的，我们将其归因于稳健的模拟环境，并仔细考虑了与研究 TM 相互作用与其他受体域隔离相关的限制。考虑到这一点，我们重新审视了其他免疫受体的结果，并期待如何应用类似的方法来了解目前几乎没有或没有结构信息的受体。

更新日期：2020-11-19

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