Characterization of Pre‐Dissociative Structures of the E6AP Trimer by All‐atom Unbiased Molecular Dynamics,Israel Journal of Chemistry

当前位置： X-MOL 学术 › Isr. J. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Characterization of Pre‐Dissociative Structures of the E6AP Trimer by All‐atom Unbiased Molecular Dynamics
Israel Journal of Chemistry ( IF 2.3 ) Pub Date : 2020-04-27 , DOI: 10.1002/ijch.202000016
Navaneet Chaturvedi _{1,

2} , Esther Nachliel ₁ , Menachem Gutman ₁

Affiliation

The activity of the E6AP protein, a member of the ubiquitin transfer system, is regulated through the association‐dissociation of its homo‐trimeric structure. Under physiologic conditions, this protein is in a mixture of mono, di and tri‐mere complexes, where the D543A mutation further destabilize the complex. These featured render this protein as an excellent model for a study of pre‐dissociation events that can be detected by applying a cluster analysis of the ∼200 ns long trajectories. The analysis of the WT complex revealed inherent divergence of the subunits, each exhibiting multiplicity of configurations that differ in their energy. Surprisingly, the trimer is more stable than the subunits. The D543A mutation caused the trimer complex to assume many equi‐potential configurations, rendering it more flexible than the subunits. The trimeric destabilization is not observed in a mutant that affects only the structure of the active site. We propose that the pre‐dissociation configurations can be identified much earlier than the structural disintegration of a proteinous complex.

中文翻译：

全原子无偏分子动力学表征E6AP三聚体的预离解结构

E6AP蛋白（泛素转移系统的成员）的活性通过其同三聚体结构的缔合-解离来调节。在生理条件下，该蛋白质以单，双和三纯复合物的混合物形式存在，其中D543A突变进一步使复合物不稳定。这些特征使该蛋白质成为研究解离前事件的极佳模型，可以通过对约200 ns长的轨迹进行聚类分析来检测该事件。WT复合物的分析显示了亚基的固有发散性，每个亚基表现出其能量不同的多种构型。出人意料的是，三聚体比亚基更稳定。D543A突变导致三聚体复合物采取许多等电势配置，使其比亚基更灵活。在仅影响活性位点结构的突变体中未观察到三聚体不稳定。我们建议可以比蛋白复合物的结构崩解更早地识别出解离前的构型。

更新日期：2020-04-27

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11