Whitley Matthew J, Lee Andrew L
Department of Biochemistry & Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Curr Protein Pept Sci. 2009 Apr;10(2):116-27. doi: 10.2174/138920309787847563.
The phenomenon of intra-protein communication is fundamental to such processes as allostery and signaling, yet comparatively little is understood about its physical origins despite notable progress in recent years. This review introduces contemporary but distinct frameworks for understanding intra-protein communication by presenting both the ideas behind them and a discussion of their successes and shortcomings. The first framework holds that intra-protein communication is accomplished by the sequential mechanical linkage of residues spanning a gap between distal sites. According to the second framework, proteins are best viewed as ensembles of distinct structural microstates, the dynamical and thermodynamic properties of which contribute to the experimentally observable macroscale properties. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for studying intra-protein communication, and the insights into both frameworks it provides are presented through a discussion of numerous examples from the literature. Distinct from mechanical and thermodynamic considerations of intra-protein communication are recently applied graph and network theoretic analyses. These computational methods reduce complex three dimensional protein architectures to simple maps comprised of nodes (residues) connected by edges (inter-residue "interactions"). Analysis of these graphs yields a characterization of the protein's topology and network characteristics. These methods have shown proteins to be "small world" networks with moderately high local residue connectivities existing concurrently with a small but significant number of long range connectivities. However, experimental studies of the tantalizing idea that these putative long range interaction pathways facilitate one or several macroscopic protein characteristics are unfortunately lacking at present. This review concludes by comparing and contrasting the presented frameworks and methodologies for studying intra-protein communication and suggests a manner in which they can be brought to bear simultaneously to further enhance our understanding of this important fundamental phenomenon.
蛋白质内通讯现象是变构和信号传导等过程的基础，尽管近年来取得了显著进展，但对其物理起源的了解仍相对较少。本综述通过介绍当代不同但独特的框架背后的思想以及对其成功与不足的讨论，来阐述对蛋白质内通讯的理解。第一个框架认为，蛋白质内通讯是通过跨越远端位点之间间隙的残基的顺序机械连接来实现的。根据第二个框架，蛋白质最好被视为不同结构微状态的集合，其动力学和热力学性质有助于实验可观察到的宏观性质。核磁共振（NMR）光谱是研究蛋白质内通讯的有力方法，通过讨论文献中的众多例子来展示它对这两个框架的见解。与蛋白质内通讯的机械和热力学考虑不同的是，最近应用的图论和网络理论分析。这些计算方法将复杂的三维蛋白质结构简化为由节点（残基）通过边（残基间“相互作用”）连接组成的简单图谱。对这些图谱的分析可以表征蛋白质的拓扑结构和网络特征。这些方法表明蛋白质是“小世界”网络，具有适度高的局部残基连接性，同时存在少量但显著的长程连接性。然而，目前遗憾的是缺乏关于这些假定的长程相互作用途径促进一种或几种宏观蛋白质特征这一诱人想法的实验研究。本综述通过比较和对比所介绍的研究蛋白质内通讯的框架和方法来结束，并提出一种可以同时运用它们以进一步增强我们对这一重要基本现象理解的方式。
