Effects of mutations on the thermodynamics of a protein folding reaction: Implications for the mechanism of formation of the intermediate and transition states
Effects of mutations on the thermodynamics of a protein folding reaction: Implications for the mechanism of formation of the intermediate and transition states
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DOI：
10.1021/bi9923510
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发表时间：
2000-03-28
期刊：
影响因子：
2.9
通讯作者：
Clarke, AR
中科院分区：
文献类型：
--
作者：
Lorch, M;Mason, JM;Clarke, AR
我们测量了 CD2.d1 折叠反应中每个步骤的热容、熵和焓的变化，并评估了核心突变对这些特性的影响。所有野生型和突变体形式都通过在限速过渡状态之前快速形成的中间状态折叠。突变对中间态和折叠态的焓都有显着影响，但在所有情况下，熵的补偿性变化都会导致较小的净自由能变化。虽然折叠状态下的焓变可归因于范德华相互作用的丧失，但已经表明中间体稳定性的变化主要由二级结构倾向的变化决定[Lorch et al. 2017]。 (1999) 生物化学 38, 1377-1385]。由此可见，β 倾向的热力学基础本质上是焓。突变对过渡态的焓和熵的影响小于基态。根据有关折叠反应中限速屏障性质的理论讨论了这种对突变的相对不敏感性。
We have measured changes in heat capacity, entropy, and enthalpy for each step in the folding reaction of CD2.d1 and evaluated the effects of core mutations on these properties. All wild-type and mutant forms fold through a rapidly formed intermediate state that precedes the rate-limiting transition state. Mutations have a pronounced effect on the enthalpy of both the intermediate and folded states, but in all cases a compensatory change in entropy results in a small net free-energy change. While the enthalpy change in the folded state can be attributed to a loss of van der Waals interactions, it has already been shown that changes in the stability of the intermediate are dominated by changes in secondary structure propensity [Lorch et al. (1999) Biochemistry 38, 1377-1385]. It follows that the thermodynamic basis of beta-propensity is enthalpic in origin. The effects of mutations on the enthalpy and entropy of the transition state are smaller than on the ground states. This relative insensitivity to mutation is discussed in the light of theories concerning the nature of the rate-limiting barrier in folding reactions.