Low Force Unfolding of a Single-Domain Protein by Parallel Pathways
Low Force Unfolding of a Single-Domain Protein by Parallel Pathways
复制标题
通过平行途径低力展开单域蛋白质
DOI：
10.1021/acs.jpcb.0c11308
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
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作者：
Zhuravlev, Pavel I.;Hinczewski, Michael;Thirumalai, D.
在单分子实验中可测量的作为机械力f的函数的蛋白质解折叠速率对数logku（f）的依赖性中的线性偏差可能由于许多原因而出现。特别是，logku（f）中的向上曲率作为f的函数，表明潜在的能量景观必须是多维的，有可能展开被平行路径包围。在这里，使用野生型β-夹心蛋白和几种突变体的SOP-SC模型进行的模拟（具有免疫球蛋白折叠）显示了解折叠动力学中的向上曲率。随着力的增加，过渡态系综的结构发生了实质性的变化，这表明解折叠途径发生了转变。我们的研究结果，结合以前的理论和实验研究，表明，结构无关的单结构域蛋白质的平行展开可以确定从logku（f）的依赖性作为力的函数（或logku[C]，其中[C]是变性剂浓度）。
Deviations from linearity in the dependence of the logarithm of protein unfolding rates, logku(f), as a function of mechanical force,f, measurable in single molecule experiments, can arise for many reasons. In particular, upward curvature in logku(f) as a function offimplies that the underlying energy landscape must be multidimensional with the possibility that unfolding ensues by parallel pathways. Here, simulations using the SOP-SC model of a wild type β-sandwich protein and several mutants, with immunoglobulin folds, show upward curvature in the unfolding kinetics. There are substantial changes in the structures of the transition state ensembles as the force is increased, signaling a switch in the unfolding pathways. Our results, when combined with previous theoretical and experimental studies, show that parallel unfolding of structurally unrelated single domain proteins can be determined from the dependence of logku(f) as a function of force (or logku[C] where [C] is the denaturant concentration).