The C-terminal domain of transcription factor RfaH: Folding, fold switching and energy landscape,Biopolymers

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The C-terminal domain of transcription factor RfaH: Folding, fold switching and energy landscape
Biopolymers ( IF 3.2 ) Pub Date : 2021-01-31 , DOI: 10.1002/bip.23420
Bahman Seifi ₁ , Stefan Wallin ₁

Affiliation

We simulate the folding and fold switching of the C-terminal domain (CTD) of the transcription factor RfaH using an all-atom physics-based model augmented with a dual-basin structure-based potential energy term. We show that this hybrid model captures the essential thermodynamic behavior of this metamorphic domain, that is, a change in the global free energy minimum from an α-helical hairpin to a 5-stranded β-barrel upon the dissociation of the CTD from the rest of the protein. Using Monte Carlo sampling techniques, we then analyze the energy landscape of the CTD in terms of progress variables for folding toward the two folds. We find that, below the folding transition, the energy landscape is characterized by a single, dominant funnel to the native β-barrel structure. The absence of a deep funnel to the α-helical hairpin state reflects a negligible population of this fold for the isolated CTD. We observe, however, a higher α-helix structure content in the unfolded state compared to results from a similar but fold switch-incompetent version of our model. Moreover, in folding simulations started from an extended chain conformation we find transiently formed α-helical structure, occurring early in the process and disappearing as the chain progresses toward the thermally stable β-barrel state.

中文翻译：

转录因子 RfaH 的 C 端结构域：折叠、折叠转换和能量景观

我们使用基于双盆结构的势能项增强的基于全原子物理的模型模拟转录因子 RfaH 的 C 末端结构域 (CTD) 的折叠和折叠转换。我们表明，该混合模型捕获了该变质域的基本热力学行为，即在 CTD 与其余部分解离时，全局自由能最小值从α螺旋发夹变为 5 链β桶的蛋白质。然后，我们使用蒙特卡罗采样技术，根据折叠到两个折叠的进度变量来分析 CTD 的能量景观。我们发现，在折叠过渡之下，能量景观的特点是单一的、主要的漏斗到原生β-桶结构。α-螺旋发夹状态没有深漏斗反映了孤立 CTD 的这种折叠的人口可以忽略不计。然而，我们观察到，与我们模型的类似但折叠开关无能版本的结果相比，展开状态下的α-螺旋结构含量更高。此外，在从延伸链构象开始的折叠模拟中，我们发现瞬时形成的α-螺旋结构，在该过程的早期发生，并随着链向热稳定的β-桶状态发展而消失。

更新日期：2021-01-31

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