Marketed Pharmaceuticals and Medical Devices Bureau, Marketed Health Products Directorate, Health Products and Food Branch, Health Canada, Canada.
Department of Pharmacology and Therapeutics, McGill University, Canada.
Neuropharmacology. 2019 Jul 1;152:4-14. doi: 10.1016/j.neuropharm.2019.01.018. Epub 2019 Jan 17.
How G protein-coupled receptors (GPCR) interact with one another remains an area of active investigation. Obligate dimers of class C GPCRs such as metabotropic GABA and glutamate receptors are well accepted, although whether this is a general feature of other GPCRs is still strongly debated. In this review, we focus on the idea that GPCR dimers and oligomers are better imagined as parts of larger metastable signalling complexes. We discuss the nature of functional oligomeric entities, their stabilities and kinetic features and how structural and functional asymmetries of such metastable entities might have implications for drug discovery. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.
G 蛋白偶联受体(GPCR)如何相互作用仍然是一个活跃的研究领域。代谢型 GABA 和谷氨酸受体等 C 类 GPCR 的必需二聚体是公认的,尽管其他 GPCR 是否具有这种特征仍存在强烈争议。在这篇综述中,我们重点讨论了这样一种观点,即 GPCR 二聚体和寡聚体更好地被视为更大的亚稳信号转导复合物的一部分。我们讨论了功能性寡聚实体的性质、它们的稳定性和动力学特征,以及这种亚稳实体的结构和功能不对称性如何对药物发现产生影响。本文是题为“受体异源二聚体及其变构受体-受体相互作用”的特刊的一部分。