Dunker A Keith, Cortese Marc S, Romero Pedro, Iakoucheva Lilia M, Uversky Vladimir N
Department of Biochemistry and Molecular Biology, and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
FEBS J. 2005 Oct;272(20):5129-48. doi: 10.1111/j.1742-4658.2005.04948.x.
Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein-protein interactions are organized into exquisitely complex networks. The architecture of protein-protein interaction networks was recently proposed to be scale-free, with most of the proteins having only one or two connections but with relatively fewer 'hubs' possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein-protein interaction in regulatory networks relies on intrinsic disorder.
蛋白质参与复杂的相互作用，这些相互作用构成了细胞许多生理过程和功能的机制基础。这些蛋白质 - 蛋白质相互作用被组织成极其复杂的网络。最近有人提出，蛋白质 - 蛋白质相互作用网络的架构是无标度的，大多数蛋白质只有一两个连接，但相对较少的“中心节点”拥有数十、数百或更多的连接。中心节点的高连接性必定会以某种方式反映在蛋白质结构中。中心蛋白的何种结构特性使其能够与大量不同的靶标相互作用？一种可能性是利用具有结合多个结构不同的伙伴能力的结合区域。这种特性可以通过在一个或两个伙伴中引入内在无序来赋予。为了说明这种贡献的价值，本综述探讨了内在无序在蛋白质网络架构中的作用。我们表明，内在无序有三种一般的贡献方式：第一，内在无序可以作为中心蛋白混杂性的结构基础；第二，内在无序的蛋白质可以与结构化的中心蛋白结合；第三，内在无序可以在功能域之间提供灵活的连接子，这些连接子促成了有助于结合多样性的机制。一个重要的研究方向将是确定调节网络中蛋白质 - 蛋白质相互作用的哪一部分依赖于内在无序。
