Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620, USA.
Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620, USA.
Curr Opin Struct Biol. 2023 Dec;83:102705. doi: 10.1016/j.sbi.2023.102705. Epub 2023 Sep 29.
Regulation of protein binding through autoinhibition commonly occurs via interactions involving intrinsically disordered regions (IDRs). These intramolecular interactions can directly or allosterically inhibit intermolecular protein or DNA binding, regulate enzymatic activity, and control the assembly of large macromolecular complexes. Autoinhibitory interactions mediated by protein disorder are inherently transient, making their identification and characterization challenging. In this review, we explore the structural and functional diversity of disorder-mediated autoinhibition for a variety of biological mechanisms, with a focus on the role of multivalency and effective concentration. We also discuss the evolution of disordered motifs that participate in autoinhibition using examples where sequence conservation varies from high to low. In some cases, identifiable motifs that are essential for autoinhibition remain intact within a rapidly evolving sequence, over long evolutionary distances. Finally, we examine the potential of AlphaFold2 to predict autoinhibitory intramolecular interactions involving IDRs.
通过自动抑制来调节蛋白质结合通常通过涉及固有无序区域 (IDR) 的相互作用来实现。这些分子内相互作用可以直接或变构地抑制分子间的蛋白质或 DNA 结合，调节酶活性，并控制大型大分子复合物的组装。由蛋白质无序介导的自动抑制相互作用本质上是短暂的，因此它们的识别和表征具有挑战性。在这篇综述中，我们探讨了结构和功能多样性的无序介导的自动抑制对于各种生物学机制，重点是多价和有效浓度的作用。我们还讨论了参与自动抑制的无序基序的进化，使用序列保守性从高到低变化的例子。在某些情况下，对于自动抑制至关重要的可识别基序在长进化距离内仍然存在于快速进化的序列中。最后，我们研究了 AlphaFold2 预测涉及 IDR 的自动抑制分子内相互作用的潜力。
