New Protein Chemical Tools for the Analysis of Cooperative Effects within Protein Interactions mediated by Ubiquitin-like Modifiers (B14)

用泛素样修饰物SUMO对底物蛋白进行翻译后修饰使底物蛋白具有额外的蛋白质相互作用界面。在蛋白质-相扑结合物的每个单元上合作结合一个伙伴蛋白质会导致细胞蛋白质网络的重新布线。我们将研究蛋白质结合界面的方向依赖协作性和变构协作性，并利用这些效应来寻找新的结合伙伴。利用这个项目中开发的新的蛋白质化学工具以及研究联盟提供的计算模拟的预测，我们将专注于相扑链的识别和与相扑转移相关的E3-连接酶复合体的形成。

Posttranslational modification of a substrate protein with the ubiquitin-like modifier SUMO equips the substrate protein with an additional protein interaction interface. Cooperative binding of a partner protein at each unit of the protein-SUMO conjugate results in the re-wiring of the cellular protein network. We will investigate both the orientation-dependent cooperativity and allosteric cooperativity of the protein binding interfaces and exploit these effects to identify new binding partners. Using new protein chemistry tools developed in this project as well as predictions from computational simulation provided in the research consortium, we will focus on the recognition of SUMO chains and the formation of the E3-ligase complexes relevant for SUMO transfer.