SUMO targeted ubiqutin ligases (STUbLs) like RNF4 or Arkadia/RNF111 recognize SUMO chains through multiple SUMO interacting motifs (SIMs). Typically, these are contained in disordered regions of these enzymes and also the individual SUMO domains of SUMO chains move relatively freely. It is assumed that binding the SIM region significantly restricts the conformational freedom of SUMO chains. Here, we present the results of extensive molecular dynamics simulations on the complex formed by the SIM2-SIM3 region of RNF4 and diSUMO3. Though our simulations highlight the importance of typical SIM-SUMO interfaces also in the multivalent situation, we observe that frequently other regions of the peptide than the canonical SIMs establish this interface. This variability regarding the individual interfaces leads to a conformationally highly flexible complex. Even though this is in contrast to previous models of the RNF4 SUMO chain interaction, we demonstrate that our simulations are clearly consistent with previous experimental results.

中文翻译：

---

二价RNF4-SIM diSUMO3相互作用的构象和界面可变性

SUMO 靶向泛素连接酶 (STUbL)，如 RNF4 或 Arkadia/RNF111，通过多个 SUMO 相互作用基序 (SIM) 识别 SUMO 链。通常，这些包含在这些酶的无序区域中，并且 SUMO 链的各个 SUMO 域也相对自由地移动。假设绑定 SIM 区域会显着限制 SUMO 链的构象自由。在这里，我们展示了对 RNF4 和 diSUMO3 的 SIM2-SIM3 区域形成的复合物进行广泛分子动力学模拟的结果。虽然我们的模拟强调了典型 SIM-SUMO 界面在多价情况下的重要性，但我们观察到，肽的其他区域经常会建立这个界面，而不是标准 SIM。这种关于单个界面的可变性导致构象高度灵活的复合体。