伴侣蛋白内部疏水效应的调节潜力
Potential for modulation of the hydrophobic effect inside chaperonins
摘要：
尽管一些体外蛋白质折叠反应具有自发性，但体内天然折叠通常需要称为伴侣蛋白的桶形多聚体复合物的参与。虽然早已知道伴侣蛋白底物在伴侣蛋白桶内隔离时折叠，但限制在该空间内促进折叠的精确机制仍然未知。在这项研究中，我们研究的可能性，伴侣蛋白介导一个有利的重组溶剂的折叠反应。首先，我们讨论了静电荷对溶剂介导的疏水力在水性环境中的影响。基于这些初始的物理参数，我们构建了一个简单的，唯象理论的密度和氢键序波动的热力学在液态水。在这个模型的框架内，我们调查的效果限制在一个类似伴侣蛋白的空腔上的水的构型自由能计算溶剂的自由能对应于不同的构象状态的空腔中的ATP驱动的原核伴侣蛋白GroEL的催化循环。我们的研究结果表明，伴侣蛋白的功能之一可能是捕获未折叠的蛋白质，并随后将它们暴露在一个微环境中，在该微环境中，疏水效应，折叠的一个关键热力学驱动力，得到增强。
英文摘要：
Despite the spontaneity of some in vitro protein folding reactions, native folding in vivo often requires the participation of barrel-shaped multimeric complexes known as chaperonins. Although it has long been known that chaperonin substrates fold upon sequestration inside the chaperonin barrel, the precise mechanism by which confinement within this space facilitates folding remains unknown. In this study, we examine the possibility that the chaperonin mediates a favorable reorganization of the solvent for the folding reaction. We begin by discussing the effect of electrostatic charge on solvent-mediated hydrophobic forces in an aqueous environment. Based on these initial physical arguments, we construct a simple, phenomenological theory for the thermodynamics of density and hydrogen bond order fluctuations in liquid water. Within the framework of this model, we investigate the effect of confinement within a chaperonin-like cavity on the configurational free energy of water by calculating solvent free energies for cavities corresponding to the different conformational states in the ATP- driven catalytic cycle of the prokaryotic chaperonin GroEL. Our findings suggest that one function of chaperonins may be to trap unfolded proteins and subsequently expose them to a micro-environment in which the hydrophobic effect, a crucial thermodynamic driving force for folding, is enhanced.
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