NEW DELOCALIZED INTERACTION THAT EXISTS IN PROTEINS AND CONTROLS FOLDING

在过去的几年中，我们已经证明RNase-(-118)缺乏6 核糖核酸酶A的羧基末端残基不是最低的吉布斯游离基 活力和高度能动性，尽管结构像原生的 包括66%的螺旋结构。我们认为，如果 传统的成对交互是集体说明的 对于核糖核酸酶-(1-118)的能量状态，导数应该具有 自由能最低。因此，为了解释我们的观察结果，我们 假设在本地存在某种离域相互作用 核糖核酸酶A来稳定结构。我们指的是这个新的 相互作用作为闭合环相互作用假设一个闭合环 由联系小组组成的小组将调解非本地化 互动。利用细胞色素c片段复合体系统 在这一节中，我们希望确定假设 控制细胞色素c折叠的一个或多个闭合环 研究了由血红素和血红素形成的杂交络合物 马、金枪鱼、假丝酵母菌和酵母的脱脂蛋白 异位L-细胞色素c.这些物种的片段被发现 是完全可交换的，但有以下例外。 金枪鱼血红素片段(1-38)H与假丝酵母菌的结合 (61-109)，但不包括假丝酵母(1-44)H和金枪鱼 (39-104)，形成结合力急剧降低的络合物。 含有酵母膏(44-108)的杂化复合体不 调查过了。通过对氨基酸序列的比较，提出了 用苏氨酸取代亮氨酸9(马的编号) 而亮氨酸98与蛋氨酸的结合较弱 金枪鱼血红素-念珠菌复合体。这个和其他 结合之前的观察结果，我们可以 指定四个闭合环1、2、3和4的位置在上面， 在亚铁血红素的左右两侧和下方， 分别进行了分析。此外，先前找到的初始二次订单 动力学相和下列一级相被指认为 分别表示闭合环路1和3的队形。循环播放 4被推测是在真核生物进化过程中添加的 原核生物中的细胞色素c。

In the previous years we have shown that RNase-(-118) lacking 6 carboxy terminal residues of RNase A is not of lowest Gibbs free energy and highly motile despite the native like structure including 66% of the helical structure. We argue that if the conventional pair-wise interactions were to collectively account for the energy state of RNase-(1-118) the derivative should have been of lowest free energy. Thus, to explain the observations we hypothesize that some delocalized interaction exists in native RNase A to stabilize the structure. We refer to this new interaction as closed loop interaction assuming that a closed loop consisting of contacting groups would mediate delocalized interaction. Using the fragment complex system of cytochrome c developed in this Section, we wish to identify the hypothetical closed loop or loops that controls folding of cytochrome c. We have investigated hybrid complexes formed from heme- and apofragments (or apoproteins) of horse, tuna, candida and yeast iso-l-cytochrome c. The fragments of these species are found to be completely exchangeable with the following exception. Combination of tuna heme fragment (1-38)H and candida apofragment (61-109), but not that of candida heme (1-44)H and tuna apofragment (39-104), forms a complex with drastically decreased binding force. Hybrid complexes containing yeast apofragment (44-108) were not investigated. Comparing the amino acid sequences it is proposed that substitutions of leucine 9 (horse numbering) with threonine and leucine 98 with methionine are responsible for the weak binding of tuna heme-candida apofragment complex. This and other observations taken together with those previous have allowed us to assign the locations of four closed loops 1,2,3 and 4 to be above, at the right and the left sides of, and below the heme, respectively. Further, the previously found initial second order kinetic phase and the following first order phase are assigned to represent formations of closed loops 1 and 3, respectively. Loop 4 is presumed to have been added during evolution of eukaryotic cytochrome c from prokaryotic species.