Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 28/30, D-48149 Münster, Germany.
Center for Multiscale Theory and Computation, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
J Phys Chem B. 2023 May 4;127(17):3806-3815. doi: 10.1021/acs.jpcb.2c08760. Epub 2023 Apr 20.
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. Comparison with previous experimental measurements clearly supports our findings and indicates that our observations can be extended to other multivalent SIM-SUMO complexes.
SUMO 靶向泛素连接酶（STUbLs），如 RNF4 或 Arkadia/RNF111，通过多个 SUMO 相互作用基序（SIM）识别 SUMO 链。通常，这些基序存在于这些酶的无规卷曲区域中，并且单个 SUMO 链的 SUMO 结构域相对自由移动。人们假设，结合 SIM 区域会显著限制 SUMO 链的构象自由度。在这里，我们展示了 RNF4 的 SIM2-SIM3 区域与 diSUMO3 形成的复合物的广泛分子动力学模拟结果。尽管我们的模拟强调了典型的 SIM-SUMO 界面在多价情况下的重要性，但我们观察到，在这种情况下，肽的非典型 SIM 区域比典型 SIM 区域更频繁地建立这种界面。这种关于单个界面的可变性导致了构象高度灵活的复合物。与之前的实验测量结果的比较清楚地支持了我们的发现，并表明我们的观察结果可以扩展到其他多价 SIM-SUMO 复合物。
