Åberg Christoffer, Duderstadt Karl E, van Oijen Antoine M
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, The Netherlands.
Zernike Institute for Advanced Materials, University of Groningen, 9747 AG Groningen, The Netherlands.
Nucleic Acids Res. 2016 Jun 2;44(10):4846-54. doi: 10.1093/nar/gkw296. Epub 2016 Apr 25.
Multi-component biological machines, comprising individual proteins with specialized functions, perform a variety of essential processes in cells. Once assembled, most such complexes are considered very stable, retaining individual constituents as long as required. However, rapid and frequent exchange of individual factors in a range of critical cellular assemblies, including DNA replication machineries, DNA transcription regulators and flagellar motors, has recently been observed. The high stability of a multi-protein complex may appear mutually exclusive with rapid subunit exchange. Here, we describe a multisite competitive exchange mechanism, based on simultaneous binding of a protein to multiple low-affinity sites. It explains how a component can be stably integrated into a complex in the absence of competing factors, while able to rapidly exchange in the presence of competing proteins. We provide a mathematical model for the mechanism and give analytical expressions for the stability of a pre-formed complex, in the absence and presence of competitors. Using typical binding kinetic parameters, we show that the mechanism is operational under physically realistic conditions. Thus, high stability and rapid exchange within a complex can be reconciled and this framework can be used to rationalize previous observations, qualitatively as well as quantitatively.
多组分生物机器由具有特定功能的单个蛋白质组成，在细胞中执行各种基本过程。一旦组装完成，大多数此类复合物被认为非常稳定，会在所需的时间内保留各个组成部分。然而，最近观察到在一系列关键的细胞组件中，包括DNA复制机器、DNA转录调节因子和鞭毛马达，单个因子会快速且频繁地交换。多蛋白复合物的高稳定性可能与亚基的快速交换相互排斥。在这里，我们描述了一种多位点竞争性交换机制，该机制基于蛋白质与多个低亲和力位点的同时结合。它解释了一个组件如何在没有竞争因子的情况下稳定地整合到复合物中，而在存在竞争蛋白的情况下能够快速交换。我们为该机制提供了一个数学模型，并给出了在没有和存在竞争者的情况下预先形成的复合物稳定性的解析表达式。使用典型的结合动力学参数，我们表明该机制在实际物理条件下是可行的。因此，复合物内的高稳定性和快速交换可以得到协调，并且这个框架可以用来定性和定量地解释以前的观察结果。
