Groundbreaking structural and spectroscopic studies of class A G protein-coupled receptors (GPCRs), such as rhodopsin and the β₂ adrenergic receptor, have provided a picture of how structural rearrangements between transmembrane helices control ligand binding, receptor activation, and effector coupling. However, the activation mechanism of other GPCR classes remains more elusive, in large part due to complexity in their domain assembly and quaternary structure. In this review, we focus on the class C GPCRs, which include metabotropic glutamate receptors (mGluRs) and gamma-aminobutyric acid B (GABA_B) receptors (GABA_BRs) most prominently. We discuss the unique biophysical questions raised by the presence of large extracellular ligand-binding domains (LBDs) and constitutive homo/heterodimerization. Furthermore, we discuss how recent studies have begun to unravel how these fundamental class C GPCR features impact the processes of ligand binding, receptor activation, signal transduction, regulation by accessory proteins, and crosstalk with other GPCRs.

对 AG 类蛋白偶联受体 (GPCR)（例如视紫质和 β ₂肾上腺素能受体）的开创性结构和光谱研究提供了跨膜螺旋之间的结构重排如何控制配体结合、受体激活和效应子偶联的图景。然而，其他 GPCR 类的激活机制仍然更加难以捉摸，这在很大程度上是由于它们的域组装和四级结构的复杂性。在这篇综述中，我们关注 C 类 GPCR，包括代谢型谷氨酸受体 (mGluR) 和 γ-氨基丁酸 B (GABA _B ) 受体 (GABA _B)Rs) 最为突出。我们讨论了由大的细胞外配体结合域 (LBD) 和组成型同源/异源二聚化的存在引起的独特的生物物理问题。此外，我们讨论了最近的研究如何开始阐明这些基本的 C 类 GPCR 特征如何影响配体结合、受体激活、信号转导、辅助蛋白调节以及与其他 GPCR 的串扰过程。