G protein-coupled receptors (GPCRs) and Nuclear Receptors (NRs) are two signaling machineries that are involved in major physiological processes and, as a consequence, in a substantial number of diseases. Therefore, they actually represent two major targets for drugs with potential applications in almost all public health issues. Full exploitation of these targets for therapeutic purposes nevertheless requires opening original avenues in drug design, and this in turn implies a better understanding of the molecular mechanisms underlying their functioning. However, full comprehension of how these complex systems function and how they are deregulated in a physiopathological context is obscured by the fact that these proteins include a substantial number of disordered regions that are central to their mechanism of action but whose structural and functional properties are still largely unexplored. In this chapter, we describe how these intrinsically disordered regions (IDR) or proteins (IDP) intervene, control and finely modulate the thermodynamics of complexes involved in GPCR and NR regulation, which in turn triggers a multitude of cascade of events that are exquisitely orchestrated to ultimately control the biological output.

G蛋白偶联受体（GPCR）和核受体（NRs）是两种信号传导机制，它们参与主要的生理过程，因此导致大量疾病。因此，它们实际上代表了在几乎所有公共卫生问题中具有潜在用途的药物的两个主要目标。然而，为了治疗目的而充分利用这些靶标需要在药物设计中开辟原始途径，而这反过来又意味着需要更好地了解其功能背后的分子机制。然而，这些蛋白质包括大量无序区域，这些区域是其作用机理的核心，但其结构和功能特性仍未得到充分开发，这一事实使人们无法完全理解这些复杂系统如何发挥作用以及如何在生理病理环境中失控。在本章中，我们将描述这些固有的无序区域（IDR）或蛋白质（IDP）如何干预，控制和精细调节参与GPCR和NR调节的复合物的热力学，进而引发大量精心策划的事件级联最终控制生物产量。