Formation of G protein-coupled receptors (GPCRs) dimers and higher order oligomers represents a key mechanism in pleiotropic signaling, yet how individual protomers function within oligomers remains poorly understood. For the Class A/rhodopsin subfamily of glycoprotein hormone receptors (GpHRs), di/oligomerization has been demonstrated to play a significant role in regulating its signaling activity at a cellular and physiological level and even pathophysiologically. Here we will describe and discuss the developments in our understanding of GPCR oligomerization, in both health and disease, from the study of this unique and complex subfamily of GPCRs with light on the luteinizing hormone receptor (LHR). Focus will be put on the results of an approach relying on the combination of atomistic modeling by protein-protein docking with super-resolution imaging. The latter could resolve single LHR molecules to ~ 8 nm resolution in functional asymmetric dimers and oligomers, using dual-color photoactivatable dyes and localization microscopy (PD-PALM). Structural modeling of functionally asymmetric LHR trimers and tetramers strongly aligned with PD-PALM-imaged spatial arrangements, identifying multiple possible helix interfaces mediating inter-protomer associations.

Diverse spatial and structural assemblies mediating GPCR oligomerization may acutely fine-tune the cellular signaling profile.

G蛋白偶联受体（GPCR）二聚体和高级寡聚体的形成代表了多效性信号传导的关键机制，但单个启动子如何在寡聚体内发挥功能仍然知之甚少。对于糖蛋白激素受体（GpHRs）的A类/视紫红质亚家族，已证明di /寡聚化在细胞和生理水平甚至病理生理学上调节其信号传导活性起着重要作用。在这里，我们将根据对黄体生成激素受体（LHR）的独特且复杂的GPCR亚家族的研究，来描述和讨论我们对GPCR寡聚在健康和疾病方面的理解发展。重点将放在依赖于通过蛋白质对接的原子建模与超分辨率成像相结合的方法的结果上。后者可以使用双色光敏染料和定位显微镜（PD-PALM）在功能不对称二聚体和低聚物中将单个LHR分子解析为〜8 nm的分辨率。功能不对称的LHR三聚体和四聚体的结构建模与PD-PALM成像的空间排列高度一致，从而确定了介导protomer关联的多个可能的螺旋界面。

介导GPCR寡聚化的不同空间和结构装配可能会微调细胞信号传导图谱。