Chemistry and Applied Biosciences Division, ETH Zürich, USI Campus, CH 6900 Lugano, Switzerland.
J Am Chem Soc. 2011 Jul 6;133(26):9976-9. doi: 10.1021/ja201500z. Epub 2011 Jun 10.
Protein-protein interactions (PPIs) are remarkably diverse and form the basis for various cellular functions. PPIs can be classified as ordered or disordered; the disordered ones do not have a well-defined structure prior to association, which is an exception to the conventional structure-function relationship. The occurrence of disordered proteins in functional roles is not explained by the conventional structure-function paradigm, and at present there is no clear understanding of the differences between the natures of these two PPIs. In this work, we studied the relationship between the kinetics and thermodynamics in PPIs to provide insights into the latter, with possible implications for the former. Analyzing the experimental data for various protein complexes, we found linear free-energy behavior with a striking kinetic difference between these two types of interactions. Binding affinities of (dis)ordered proteins are correlated with their (association) dissociation rates. Our observation, combined with the correspondence between biological activity and affinity, suggests that selection pressure on the dissociation or association kinetics in a functional context necessitates the presence of (dis)order in the structure.
蛋白质-蛋白质相互作用 (PPIs) 非常多样化，构成了各种细胞功能的基础。PPIs 可以分为有序和无序两种；无序的蛋白质在结合之前没有明确的结构，这是对传统结构-功能关系的一个例外。无序蛋白质在功能作用中的出现不能用传统的结构-功能范式来解释，目前对这两种 PPI 的性质差异还没有清晰的认识。在这项工作中，我们研究了 PPIs 中的动力学和热力学之间的关系，以期深入了解后者，并可能对前者产生影响。通过分析各种蛋白质复合物的实验数据，我们发现了线性自由能行为，这两种相互作用在动力学上存在显著差异。（无序）蛋白质的结合亲和力与其（缔合）解离速率相关。我们的观察结果，结合生物活性与亲和力之间的对应关系，表明在功能背景下对解离或缔合动力学的选择压力需要结构中存在（无序）。
