2021年11月18日，《科学》杂志在线发表了来自美国斯克利普斯研究所Kirill A. Martemyanov、印度理工学院Appu K. Singh等研究人员的合作成果
研究人员报告了人类GPR158单独以及与RGS信号复合物结合的结构，这些结构是用单粒子冷冻电镜（cryoEM）测定的。这些结构显示了一个由一对磷脂稳定的同源二聚体组织，以及细胞外Cache结构域的存在，这是G蛋白偶联受体（GPCR）中一个不寻常的配体结合结构域。研究人员进一步证明了GPR158与RGS7-Gβ5偶联的结构基础。这些结果共同提供了对孤儿受体的不寻常生物学和GPCR-RGS复合体形成的见解。
据悉，GPR158是一个孤儿GPCR，在大脑中高度表达，它控制突触的形成和功能。GPR158也被认为与抑郁症、致癌和认知有关。然而，GPR158的结构组织和信号传导机制在很大程度上是未知的。
附：英文原文
Title: Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex
Author: Dipak N. Patil, Shikha Singh, Thibaut Laboute, Timothy S. Strutzenberg, Xingyu Qiu, Di Wu, Scott J. Novick, Carol V. Robinson, Patrick R. Griffin, John F. Hunt, Tina Izard, Appu K. Singh, Kirill A. Martemyanov
Issue&Volume: 2021-11-18
Abstract: GPR158 is an orphan G-protein-coupled receptor (GPCR) highly expressed in the brain where it controls synapse formation and function. GPR158 has also been implicated in depression, carcinogenesis and cognition. However, the structural organization and signaling mechanisms of GPR158 are largely unknown. Here, we report structures of the human GPR158 alone and bound to an RGS signaling complex, determined using single-particle cryo-electron microscopy (cryoEM). The structures reveal a homodimeric organization stabilized by a pair of phospholipids and the presence of an extracellular Cache domain, an unusual ligand-binding domain in GPCRs.-. We further demonstrate the structural basis of GPR158 coupling to RGS7-Gβ5. Together, these results provide insights into the unusual biology of orphan receptors and the formation of GPCR-RGS complexes.
DOI: abl4732
Source: https://www.science.org/doi/10.1126/science.abl4732