Haynie D T, Freire E
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
Proteins. 1993 Jun;16(2):115-40. doi: 10.1002/prot.340160202.
Certain partly ordered protein conformations, commonly called "molten globule states," are widely believed to represent protein folding intermediates. Recent structural studies of molten globule states of different proteins have revealed features which appear to be general in scope. The emerging consensus is that these partly ordered forms exhibit a high content of secondary structure, considerable compactness, nonspecific tertiary structure, and significant structural flexibility. These characteristics may be used to define a general state of protein folding called "the molten globule state," which is structurally and thermodynamically distinct from both the native state and the denatured state. Despite extensive knowledge of structural features of a few molten globule states, a cogent thermodynamic argument for their stability has not yet been advanced. The prevailing opinion of the last decade was that there is little or no enthalpy difference or heat capacity difference between the molten globule state and the unfolded state. This view, however, appears to be at variance with the existing database of protein structural energetics and with recent estimates of the energetics of denaturation of alpha-lactalbumin, cytochrome c, apomyoglobin, and T4 lysozyme. We discuss these four proteins at length. The results of structural studies, together with the existing thermodynamic values for fundamental interactions in proteins, provide the foundation for a structural thermodynamic framework which can account for the observed behavior of molten globule states. Within this framework, we analyze the physical basis for both the high stability of several molten globule states and the low probability of other potential folding intermediates. Additionally, we consider, in terms of reduced enthalpy changes and disrupted cooperative interactions, the thermodynamic basis for the apparent absence of a thermally induced, cooperative unfolding transition for some molten globule states.
某些部分有序的蛋白质构象，通常被称为“熔球态”，被广泛认为代表蛋白质折叠中间体。最近对不同蛋白质熔球态的结构研究揭示了一些似乎具有普遍意义的特征。新出现的共识是，这些部分有序的形式具有高含量的二级结构、相当的紧凑性、非特异性三级结构以及显著的结构灵活性。这些特征可用于定义一种称为“熔球态”的蛋白质折叠一般状态，它在结构和热力学上与天然态和变性态都不同。尽管对少数熔球态的结构特征有广泛了解，但尚未提出关于它们稳定性的有说服力的热力学论据。过去十年的主流观点是，熔球态与未折叠态之间几乎没有或没有焓差或热容差。然而，这种观点似乎与现有的蛋白质结构能量学数据库以及最近对α-乳白蛋白、细胞色素c、脱辅基肌红蛋白和T4溶菌酶变性能量学的估计不一致。我们详细讨论这四种蛋白质。结构研究的结果，连同蛋白质中基本相互作用的现有热力学值，为一个结构热力学框架提供了基础，该框架可以解释熔球态的观察行为。在这个框架内，我们分析了几种熔球态高稳定性和其他潜在折叠中间体低概率的物理基础。此外，我们从降低的焓变和破坏的协同相互作用方面考虑了一些熔球态明显不存在热诱导协同解折叠转变的热力学基础。
