Lazim Raudah, Suh Donghyuk, Lee Jai Woo, Vu Thi Ngoc Lan, Yoon Sanghee, Choi Sun
Global AI Drug Discovery Center, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
Int J Mol Sci. 2021 Mar 22;22(6):3241. doi: 10.3390/ijms22063241.
G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to attract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein-protein interactions (PPI).
G蛋白偶联受体（GPCR）的寡聚化虽然存在争议，但仍继续吸引着研究人员的关注。众多实验研究已证实GPCR二聚体的存在，并且二聚化在生理功能实现中的相关性增强了这一概念作为潜在治疗靶点的吸引力。GPCR作为单一实体，一直是针对多种疾病（如癌症、炎症、心脏和呼吸系统疾病）进行药物设计目标研究的主要对象。二聚体的存在拓宽了GPCR功能的研究范围，揭示了新的信号通路，这些通路可成为疾病发病机制的靶点，而当GPCR仅以单体形式被看待时，此前并未有相关报道。本综述将重点介绍GPCR二聚化的几个方面，包括通过代谢型谷氨酸受体和γ-氨基丁酸B受体的三维全长结构的最新解析，对C类GPCR激活的变构调节的结构阐释总结，以及二聚化在GPCR功能和变构调节修饰中的作用。随着计算方法在GPCR研究中的影响力不断增加，我们还将回顾最近用于绘制蛋白质-蛋白质相互作用（PPI）的计算工具。
