THE PRINCIPLES THAT GOVERN PROTEIN FOLDING--THE SECOND HALF OF THE GENETIC CODE

基于以前的研究，我们假设在折叠之后 例如，葡萄球菌核酸酶的原子间 相互作用将在全球范围内耦合，以产生额外的力 改变折叠和展开之间的平衡，有利于 折叠，并且这种耦合将在一条线的基础上发生 三个原子之间的接触形成一条闭合的曲线- 空间结构。全球范围内调制的结果 耦合将是从一个 从构象能态到另一种构象能态会涉及到 在整个过程中约束原子位置的力的变化 这个结构。我们已经用一个模型检验了这一假设 由血红素形成的两种异构体络合物I和II系统 马细胞色素c.WE的(1-38)H片段和脱脂蛋白 研究1)相互转化的动力学和热力学 I型和II型复合铁氧体(1-38)H-(1-104)；2) 共结合布居；3)解离速率 铁和铁(1-38)H-(39-104)(模拟II型) 以及4)695 mm吸收带的热跃迁 和生物活性。结果表明：a)相互转化 在两种形式的络合铁氧体(1-38)H-(104)之间发生 而不经历解离，并与热焓有关 有利于类型I的变化和有利于类型II的熵变；b) 共结合布居与II型相关；以及c)氧化还原 血红素的状态似乎影响热力学关系 在这两种形式之间。结果表明，“内部-- 在铁离子类型I型和铁型II型之间的分子翻转将 分别建立了这两者的玻尔兹曼分布 不同的能量状态，I类形式具有更强的 原子间相互作用和第二类更明显的内部 动议。由于该模型本质上是一个精确的两态系统 同分异构体的组成、测量的热焓和测量的熵 变化可以毫不含糊地解释为与变化有关 内部运动，即约束原子的力的变化 分布在结构中的位置，揭示了新的主要来源 蛋白质折叠的热变和熵变。

Based on the previous studies, we hypothesize that after folding of, for example, staphylococcal nuclease the interatomic interactions would be globally coupled to generate extra force for shifting the equilibrium between folding and unfolding in favor of folding and that such coupling would occur on the basis of a line of contacting atoms forming a closed curve in the three- dimensional structure. A result of modulation of this global coupling would be that transformation from one of the conformational energy states to another would involve concerted changes of forces constraining the atomic positions throughout the structure. We have tested this hypothesis using a model system of two isomeric complexes type I and II formed from heme fragment (1-38)H and apoprotein of horse cytochrome c. We investigated 1) kinetics and thermodynamics of interconversion between type I and II forms of complex ferro(1-38)H-(1-104); 2) the CO-binding population; 3) the rate of dissociation of complexes ferri- and ferro(1-38)H-(39-104) (mimicking type II form); and 4) thermal transition of the 695mm absorption band and biological activity. The results indicate a) interconversion between the two forms of complex ferro(1-38)H-(104) occurs without going through dissociation and is associated with enthalpy change favoring type I and entropy change favoring type II; b) the CO-binding population correlates with type II; and c) the redox state of heme appears to influence the thermodynamic relatinship between the two forms. The results suggest that "intra- molecular" flip between ferro-type I and ferro-type II forms would establish the Boltzmann distribution of these two distinctly different energy states, type I form having more strengthened interatomic interactions and type II more pronounced internal motion. Since this model is an exact two-state system by virtue of isomeric complexes, the measured enthalpy and entropy changes can be unambiguously interpreted as relating to changes of internal motion, i.e. changes of forces constraining atomic positions distributed in the structure, revealing new major sources of enthalpy and entropy changes for protein folding.