Kumar S, Nussinov R
Laboratory of Experimental and Computational Biology, NCI-Frederick, Maryland 21702, USA.
Cell Mol Life Sci. 2001 Aug;58(9):1216-33. doi: 10.1007/PL00000935.
Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein. At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change between the folded and unfolded states of the protein.
近年来，嗜热和超嗜热生物蛋白质的序列和结构信息呈爆发式增长。许多超嗜热古菌的完整基因组序列已可得。在此，我们综述了一些关于蛋白质热稳定性的近期研究以及我们实验室的工作。大量的序列和结构因素被认为有助于提高这些生物来源蛋白质的固有热稳定性。最一致的因素是表面环缺失、带有支链侧链的疏水残基出现频率增加以及带电残基比例增加，同时不带电的极性残基比例降低。诸如盐桥及其网络等静电相互作用对蛋白质稳定性的能量贡献可能是稳定的，也可能是不稳定的。对于超嗜热蛋白质，这种贡献大多是稳定的。从宏观上看，静电相互作用的改善以及支链非极性残基对疏水核心的强化增加了嗜热蛋白质折叠态与未折叠态之间的焓变。同时，表面环缺失导致蛋白质折叠态与未折叠态之间的构象熵降低以及热容变化减小。
