Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Protein Sci. 2011 Feb;20(2):336-40. doi: 10.1002/pro.564.
Repeat proteins comprise tandem arrays of a small structural motif. Their structure is defined and stabilized by interactions between residues that are close in the primary sequence. Several studies have investigated whether their structural modularity translates into modular thermodynamic properties. Tetratricopeptide repeat proteins (TPRs) are a class in which the repeated unit is a 34 amino acid helix-turn-helix motif. In this work, we use differential scanning calorimetry (DSC) to study the equilibrium stability of a series of TPR proteins with different numbers of an identical consensus repeat, from 2 to 20, CTPRa2 to CTPRa20. The DSC data provides direct evidence that the folding/unfolding transition of CTPR proteins does not fit a two-state folding model. Our results confirm and expand earlier studies on TPR proteins, which showed that apparent two-state unfolding curves are better fit by linear statistical mechanics models: 1D Ising models in which each repeat is treated as an independent folding unit.
重复蛋白由小结构基序的串联排列组成。它们的结构通过在一级序列中接近的残基之间的相互作用来定义和稳定。已有几项研究调查了它们的结构模块化是否转化为模块化热力学性质。四肽重复蛋白（TPR）是其中一个重复单元为 34 个氨基酸的螺旋-转角-螺旋基序的类别。在这项工作中，我们使用差示扫描量热法（DSC）研究了一系列具有不同数量相同共识重复的 TPR 蛋白的平衡稳定性，从 2 到 20，CTPRa2 到 CTPRa20。DSC 数据提供了直接证据，证明 CTPR 蛋白的折叠/去折叠转变不符合二态折叠模型。我们的结果证实并扩展了早期关于 TPR 蛋白的研究，这些研究表明，明显的二态展开曲线更适合线性统计力学模型：每个重复都被视为独立折叠单元的 1D Ising 模型。
