Dipartimento di Scienze Biochimiche, Universită di Roma Sapienza, Italy.
Curr Protein Pept Sci. 2010 Feb;11(1):2-36. doi: 10.2174/138920310790274653.
Cooperative interactions within biological macromolecules are of fundamental physiological relevance and have been studied in great detail. Yet, even in the best investigated case of oxygen binding by hemoglobin, our understanding of the structural and thermodynamic bases of cooperativity is far from satisfactory. Several theoretical models have been proposed to explain cooperative O2 binding to hemoglobin, among which the two-state model by Monod, Wyman and Changeux, has been the most successful and the most thoroughly tested. This model explains the functional properties of hemoglobin as resulting from the equilibrium of two quaternary conformations, named R and T, characterized by different ligand affinity, and is capable of very accurate (but not always exact) predictions. This review focuses on the experiments carried out to test the models of cooperativity, and especially the two-state model, and identifies two major deviations, or groups of deviations, between the predictions of this model and the actual experimental results, namely (i) the changes in the behaviour of the T- and R-state due to solvent components; (ii) the appearance of R-like reactivity under experimental conditions in which the T-state should be largely prevalent. Modern models of cooperativity, devised to account for these discrepancies while maintaining the basic two-state hypothesis of Monod, Wyman and Changeux, are also reviewed.
生物大分子内的协同相互作用具有重要的生理相关性，并已得到深入研究。然而，即使在血红蛋白氧结合这一研究得最好的例子中，我们对协同作用的结构和热力学基础的理解仍远未令人满意。已经提出了几种理论模型来解释血红蛋白的协同 O2 结合，其中 Monod、Wyman 和 Changeux 的二态模型是最成功和最彻底测试的模型。该模型将血红蛋白的功能性质解释为两种四级构象（称为 R 和 T）之间的平衡的结果，这些构象具有不同的配体亲和力，并能够进行非常准确（但并不总是完全准确）的预测。本综述重点介绍了用于检验协同作用模型，特别是二态模型的实验，并确定了该模型的预测与实际实验结果之间的两个主要偏差，即：（i）溶剂成分引起的 T-态和 R-态行为变化；（ii）在 T-态应占主导地位的实验条件下出现类似于 R-态的反应性。还回顾了为解释这些差异而设计的现代协同作用模型，同时保持 Monod、Wyman 和 Changeux 的基本二态假设。
