Jaenicke R
Institute of Biophysics and Physical Biochemistry, University of Regensburg, Germany.
Ciba Found Symp. 1991;161:206-16; discussion 217-21.
Proteins show only marginal free energies of stabilization. Mutative adaptations to extremes of physical conditions (high temperature, pressure and salt concentration) tend to maintain 'corresponding states' regarding overall topology, flexibility and hydration. Since enhanced stability requires only minute local changes in the structure of a given protein, general strategies of adaptation cannot be established. Apart from alterations at the protein level, extrinsic factors such as ions, cofactors or specific ligands may serve to enhance in vivo and in vitro protein stability. Protein folding and association reflect the hierarchy of protein structure, with the formation of secondary/supersecondary structure, subdomains/domains and structured monomers as consecutive steps. The process requires highly specified environmental conditions; e.g. active mesophilic or halophilic proteins cannot be expressed in thermophilic and non-halophilic hosts. On the other hand, a given protein may tolerate extreme sequence variability without substantially altering its three-dimensional structure and stability. Significant rate-determining steps in the overall reaction, that is, formation of disulphide bridges, proline isomerization and oligomerization, are catalysed by specific enzymes or directed by 'helper proteins' (protein disulphide isomerase, peptidyl-prolyl cis-trans isomerase and chaperones). Physiological stress conditions, (site-directed) mutations, and in vitro studies may be used to unravel the significance of the three 'shuffling reactions'.
蛋白质仅表现出微弱的稳定自由能。对极端物理条件（高温、高压和盐浓度）的突变适应往往会在整体拓扑结构、柔韧性和水合作用方面维持“相应状态”。由于增强稳定性仅需要给定蛋白质结构发生微小的局部变化，因此无法确立通用的适应策略。除了蛋白质水平的改变外，诸如离子、辅因子或特定配体等外在因素可能有助于增强体内和体外蛋白质的稳定性。蛋白质折叠和缔合反映了蛋白质结构的层次结构，二级/超二级结构、亚结构域/结构域和结构化单体的形成是连续的步骤。该过程需要高度特定的环境条件；例如，活性嗜温或嗜盐蛋白质无法在嗜热和非嗜盐宿主中表达。另一方面，给定的蛋白质可能耐受极端的序列变异性而基本不改变其三维结构和稳定性。整体反应中重要的限速步骤，即二硫键的形成、脯氨酸异构化和寡聚化，由特定酶催化或由“辅助蛋白”（蛋白质二硫键异构酶、肽基脯氨酰顺反异构酶和伴侣蛋白）指导。生理应激条件、（定点）突变和体外研究可用于揭示三种“改组反应”的重要性。
