Quantitative Biophysical Characterization of Intrinsically Disordered Proteins
Quantitative Biophysical Characterization of Intrinsically Disordered Proteins
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DOI：
10.1021/bi501460a
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发表时间：
2015-02-17
期刊：
影响因子：
2.9
通讯作者：
Showalter, Scott A.
中科院分区：
文献类型：
--
作者：
Gibbs, Eric B.;Showalter, Scott A.
内含子无序蛋白（IDP）被广泛定义为不能协同折叠成空间或时间稳定结构的蛋白质区域。最近的研究有力地支持了这样的假设，即结构紊乱的保守功能作用使得IDP独特地能够在诸如细胞信号传导和转录的生物过程中发挥作用。最近，严格的机械生物化学和定量生物物理学的无序系统的应用频率显着增加。例如，蛋白质Encoding数据库（pE-DB）的推出表明，现在存在使用实验数据来完善IDP天然状态结构模型的潜力。然而，现在需要严格评估哪些可观测量对这些集合的约束最强和最小。最重要的是，在过去的几年里，试图将结构紊乱与功能联系起来的生物化学和生物物理学研究的数量出现了强劲增长。从平衡热力学的角度来看，如果可以概括的话，显然需要评估IDP相互作用中疏水力与静电力的相对重要性。最后，动力学机制，调用构象选择和/或诱导适合经常被用来表征耦合IDP折叠和结合，虽然这些模型的应用通常是建立在热力学观测。最近，通过严格的动力学实验已经测试了更多的内在无序系统的反应速率和动力学机制。出于这些令人兴奋的进展，在这里，我们提供了一个审查和招股说明书的IDP结构，热力学和动力学的定量研究。
Intrinsically disordered proteins (IDPs) are broadly defined as protein regions that do not cooperatively fold into a spatially or temporally stable structure. Recent research strongly supports the hypothesis that a conserved functional role for structural disorder renders IDPs uniquely capable of functioning in biological processes such as cellular signaling and transcription. Recently, the frequency of application of rigorous mechanistic biochemistry and quantitative biophysics to disordered systems has increased dramatically. For example, the launch of the Protein Ensemble Database (pE-DB) demonstrates that the potential now exists to refine models for the native state structure of IDPs using experimental data. However, rigorous assessment of which observables place the strongest and least biased constraints on those ensembles is now needed. Most importantly, the past few years have seen strong growth in the number of biochemical and biophysical studies attempting to connect structural disorder with function. From the perspective of equilibrium thermodynamics, there is a clear need to assess the relative significance of hydrophobic versus electrostatic forces in IDP interactions, if it is possible to generalize at all. Finally, kinetic mechanisms that invoke conformational selection and/or induced fit are often used to characterize coupled IDP folding and binding, although application of these models is typically built upon thermodynamic observations. Recently, the reaction rates and kinetic mechanisms of more intrinsically disordered systems have been tested through rigorous kinetic experiments. Motivated by these exciting advances, here we provide a review and prospectus for the quantitative study of IDP structure, thermodynamics, and kinetics.