Cai Xin, Wang Dexiu, Zhang Rumin, Chen Yanchun, Chen Jing
School of Basic Medical Sciences, Weifang Medical University, Weifang 261053, China.
Neurobiology Institute, Jining Medical University, Jining, Shandong 272067, China.
Drug Discov Today. 2023 Jan;28(1):103419. doi: 10.1016/j.drudis.2022.103419. Epub 2022 Oct 26.
G-protein-coupled receptors (GPCRs) can form homodimers or heterodimers that modulate specific signal transduction pathways to regulate a wide range of physiological and pathological functions. As such, GPCR dimers are novel drug targets for disorders including depression, hypertension, diabetes, and vascular dementia. The interaction between two receptors in a GPCR dimer involves a conformational change in the transmembrane domain (TMD). It has been demonstrated that the TMD has an important role in GPCR dimer formation and stability in vitro and in vivo. Moreover, increasing evidence shows that the TMD of GPCRs affects the function of dimers. Therefore, the TMD of GPCRs is an emerging target for the development of drugs to treat diseases that involve GPCR dimerization.
G蛋白偶联受体（GPCRs）可形成同二聚体或异二聚体，这些二聚体调节特定的信号转导途径，以调控广泛的生理和病理功能。因此，GPCR二聚体是包括抑郁症、高血压、糖尿病和血管性痴呆等疾病的新型药物靶点。GPCR二聚体中两个受体之间的相互作用涉及跨膜结构域（TMD）的构象变化。已经证明，TMD在体外和体内的GPCR二聚体形成及稳定性中发挥重要作用。此外，越来越多的证据表明，GPCRs的TMD会影响二聚体的功能。因此，GPCRs的TMD是开发治疗涉及GPCR二聚化疾病药物的一个新兴靶点。
