Compliant mechanical response of the ultrafast folding protein EnHD under force
Compliant mechanical response of the ultrafast folding protein EnHD under force
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DOI：
10.1038/s42005-022-01125-5
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发表时间：
2023-01-12
影响因子：
5.5
通讯作者：
Perez-Jimenez，Raul
中科院分区：
文献类型：
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作者：
Reifs，Antonio;Ortiz，Irene Ruiz;Perez-Jimenez，Raul
超快折叠蛋白已成为蛋白质折叠动力学研究的重要范例。由于其能量势垒低和动力学快，它们适合通过实验和模拟进行研究。然而，在这些系统上进行单分子力谱实验具有挑战性，因为这些蛋白质不提供机械稳定性更高的蛋白质的机械指纹特征，这使得提取有关分子折叠动力学的信息变得困难。在这里，我们通过单分子原子力显微镜实验研究了超快蛋白 Engrailed 同源域 (EnHD) 的展开。 EnHD 的恒速实验会导致顺应性蛋白质典型的无特征转变。然而，在力斜坡模式下，我们恢复了 S 形曲线，我们将其解释为一种非常顺应的蛋白质，可以在边缘屏障上折叠和展开多次。这得到了简单的理论模型和粗粒度分子模拟的支持。我们的结果显示了力调节超快折叠蛋白质的展开动力学的能力。
Ultrafast folding proteins have become an important paradigm in the study of protein folding dynamics. Due to their low energetic barriers and fast kinetics, they are amenable for study by both experiment and simulation. However, single molecule force spectroscopy experiments on these systems are challenging as these proteins do not provide the mechanical fingerprints characteristic of more mechanically stable proteins, which makes it difficult to extract information about the folding dynamics of the molecule. Here, we investigate the unfolding of the ultrafast protein Engrailed Homeodomain (EnHD) by single-molecule atomic force microscopy experiments. Constant speed experiments on EnHD result in featureless transitions typical of compliant proteins. However, in the force-ramp mode we recover sigmoidal curves that we interpret as a very compliant protein that folds and unfolds many times over a marginal barrier. This is supported by a simple theoretical model and coarse-grained molecular simulations. Our results show the ability of force to modulate the unfolding dynamics of ultrafast folding proteins.