Munson M, Anderson K S, Regan L
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Fold Des. 1997;2(1):77-87. doi: 10.1016/S1359-0278(97)00008-4.
The dimeric four-helix-bundle protein Rop folds and unfolds extremely slowly. To understand the molecular basis for the slow kinetics, we have studied the folding and unfolding of wild-type Rop and a series of hydrophobic core mutants.
Mutation of the hydrophobic core creates stable, dimeric, and wild-type-like proteins with dramatically increased rates of both folding and unfolding. The increases in rates are dependent upon the number and position of repacked residues within the hydrophobic core.
Rop folds by a rapid collision of monomers to form a dimeric intermediate with substantial helical content, followed by a slow rearrangement to the final native structure. Rop unfolding is a single extremely slow kinetic phase. The slow steps of both folding and unfolding are dramatically increased by hydrophobic core replacements, suggesting that their main effect is to substantially decrease the energy of the transition state.
二聚体四螺旋束蛋白Rop的折叠和去折叠极其缓慢。为了理解其缓慢动力学的分子基础，我们研究了野生型Rop和一系列疏水核心突变体的折叠与去折叠过程。
疏水核心的突变产生了稳定的、二聚体的且类似野生型的蛋白，其折叠和去折叠速率都显著增加。速率的增加取决于疏水核心内重新排列的残基的数量和位置。
Rop通过单体的快速碰撞折叠形成具有大量螺旋结构的二聚体中间体，随后缓慢重排至最终的天然结构。Rop去折叠是一个极其缓慢的单一动力学阶段。疏水核心替换显著加快了折叠和去折叠的慢步骤，这表明其主要作用是大幅降低过渡态的能量。
