Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
PLoS Comput Biol. 2012;8(10):e1002704. doi: 10.1371/journal.pcbi.1002704. Epub 2012 Oct 4.
Protein-protein interactions play an important role in all biological processes. However, the principles underlying these interactions are only beginning to be understood. Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation, regulate transport and other functions. As such, it interacts with and is recognised by a multitude of other proteins. We have conducted molecular dynamics simulations of ubiquitin in complex with 11 different binding partners on a microsecond timescale and compared them with ensembles of unbound ubiquitin to investigate the principles of their interaction and determine the influence of complex formation on the dynamic properties of this protein. Along the main mode of fluctuation of ubiquitin, binding in most cases reduces the conformational space available to ubiquitin to a subspace of that covered by unbound ubiquitin. This behaviour can be well explained using the model of conformational selection. For lower amplitude collective modes, a spectrum of zero to almost complete coverage of bound by unbound ensembles was observed. The significant differences between bound and unbound structures are exclusively situated at the binding interface. Overall, the findings correspond neither to a complete conformational selection nor induced fit scenario. Instead, we introduce a model of conformational restriction, extension and shift, which describes the full range of observed effects.
蛋白质-蛋白质相互作用在所有生物过程中都起着重要作用。然而，这些相互作用的原理才刚刚开始被理解。泛素是一种小的信号蛋白，通过共价键与不同的蛋白质结合，以标记它们进行降解、调节运输和其他功能。因此，它与许多其他蛋白质相互作用并被其识别。我们已经在微秒时间尺度上对泛素与 11 种不同结合伴侣的复合物进行了分子动力学模拟，并将其与未结合的泛素集合进行了比较，以研究它们相互作用的原理，并确定复合物形成对这种蛋白质动态特性的影响。在泛素的主要波动模式中，在大多数情况下，结合将泛素的构象空间减少到未结合的泛素所覆盖的子空间。这种行为可以使用构象选择模型很好地解释。对于较低幅度的集体模式，观察到从几乎完全覆盖到零的结合和未结合集合的谱。结合和未结合结构之间的显著差异仅位于结合界面处。总体而言，这些发现既不符合完全的构象选择，也不符合诱导契合的情况。相反，我们引入了构象限制、扩展和移位的模型，该模型描述了所观察到的全部效果。
