多肽结形成的能量成本及其折叠后果。
The energy cost of polypeptide knot formation and its folding consequences.
机构信息
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Independencia, Santiago, 8380494, Chile.
Departamento Académico de Ciencias Exactas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porras, Lima-31, 15102, Peru.
出版信息
Nat Commun. 2017 Nov 17;8(1):1581. doi: 10.1038/s41467-017-01691-1.
Knots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain-an event that can potentially impair its folding-and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to form a trefoil knot in the denatured state of a polypeptide chain of 120 residues is 5.8 ± 1 kcal mol. Monte Carlo dynamics of random chains predict this value, indicating that the free energy cost of knot formation is of entropic origin. This cost is predicted to remain above 3 kcal mol for denatured proteins as large as 900 residues. Therefore, we conclude that naturally knotted proteins cannot attain their knot randomly in the unfolded state but must pay the cost of knotting through contacts along their folding landscape.
纽结是链的自然拓扑结构。然而，人们对多肽链中自发形成纽结的现象知之甚少——这种现象可能会阻碍其折叠——以及纽结对蛋白质稳定性和折叠动力学的影响也知之甚少。在这里，我们使用光镊表明，在 120 个残基的多肽链变性状态下形成三叶结的自由能成本为 5.8±1 kcal/mol。随机链的蒙特卡罗动力学预测了这个值，表明纽结形成的自由能成本来源于熵。预测表明，对于变性蛋白，这个成本在 3 kcal/mol 以上，其大小可达 900 个残基。因此，我们得出结论，天然纽结蛋白不能在未折叠状态下随机形成纽结，而是必须通过沿其折叠景观的接触来支付纽结的成本。
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