As the largest family of cell surface receptors, G protein-coupled receptors (GPCRs) represent an important strategic class of therapeutic targets. Attaining a clearer perspective of how such signaling complexes set molecular events in motion could have significant impact on our understanding and treatment of human diseases. As such, many experimental approaches have set out to better understand signaling networks associated with individual receptors to understand signaling architectures and their relationship to signaling outcomes. However, designing in vitro assays aimed at addressing signaling events downstream of single GPCRs must also take into account their propensity to form homo- and heterooligomeric complexes. In the context of GPCR oligomers, physical interactions with a partner protein can have a number of potential consequences, which we will explore in this review. We will also discuss methods used to identify putative dimer partners as well as the various techniques used to study the functional consequences of such complex formation. Since the full functional significance and physiological relevance of GPCR oligomers remains incompletely understood, owing in part to technical limitations, new tools to elucidate molecular mechanisms underlying allosteric co-regulation occurring between two GPCRs are required. Accordingly, using the example of the FP/AT₁R heterodimer, we discuss the potential of the FlAsH-BRET approach as a simple tool to reveal how allosteric information is transmitted via conformational rearrangements within putative GPCR complexes and as a means to deorphanize receptors.

作为细胞表面受体的最大家族，G蛋白偶联受体（GPCR）代表了重要的治疗靶点策略类。对这种信号复合物如何使分子事件发生运动的更清晰认识可能会对我们对人类疾病的理解和治疗产生重大影响。这样，许多实验方法已经开始更好地理解与各个受体相关的信号网络，以了解信号结构及其与信号结果的关系。但是，体外设计旨在解决单个GPCR下游信号转导事件的分析也必须考虑其形成同型和异型寡聚复合物的倾向。在GPCR寡聚物的背景下，与伴侣蛋白的物理相互作用可能会产生许多潜在的后果，我们将在本综述中进行探讨。我们还将讨论用于识别推定的二聚体伴侣的方法，以及用于研究这种复杂形式的功能后果的各种技术。由于对GPCR低聚物的全部功能意义和生理相关性仍未完全了解，部分是由于技术上的限制，因此需要新的工具阐明两个GPCR之间发生的变构共同调控的分子机制。因此，以FP / AT ₁为例R异二聚体，我们讨论FlAsH-BRET方法的潜力，作为一种简单的工具来揭示变构信息是如何通过假定的GPCR复合物中的构象重排传递的，以及作为使受体脱孤子的一种手段。