Regulatory mechanism dictating GPSM3 selectivity toward G protein-coupled receptor complex

G蛋白偶联受体（GPCR）是大型变构机器，因为它们动态地结合细胞外和细胞内配体或蛋白质以形成传播构象受限的细胞信号的复合物。这种相互变构系统是GPCR信号传导的多维性和异质性的基础。GPCR作为异源三聚体G蛋白（Gαβγ）的催化激活剂，通过将GTP交换为Gα亚基上的结合GDP。这种鸟嘌呤核苷酸交换因子活性是G蛋白循环的初始步骤，并决定各种细胞内信号传导途径的开始。调节蛋白和辅助蛋白通过控制信号幅度和持续时间或作为G蛋白非依赖性信号传导的支架来微调细胞内信号转导。最新的信号调节模式之一是从发现无活性Gαi/o亚基和GoLoco（也称为GPR）基序蛋白之间的关联中认识到的，这种关联排除了Gα·GDP/Gβγ无活性异源三聚体的重组。

G protein-coupled receptor (GPCRs) are large allosteric machines in that they dynamically bind extracellular and intracellular ligands or proteins to form complexes that propagate conformationally restricted cellular signals. This reciprocal allosteric system is the basis of the pluridimensional and heterogenicity of GPCR signaling. GPCRs serve as catalytic activators of heterotrimeric G-proteins (Gαβγ) by exchanging GTP for the bound GDP on the Gα subunit. This guanine nucleotide exchange factor activity is the initial step in the G-protein cycle and determines the onset of various intracellular signaling pathways. Regulatory and accessory proteins fine-tune the intracellular signals transduced by controlling the signal amplitude and duration or acting as a scaffold for G protein-independent signaling. One of the most recent modes of signaling regulation was recognized from the discovery of the association between inactive Gαi/o subunits and GoLoco (also called GPR) motif proteins – an association that excludes reformation of the Gα·GDP/Gβγ inactive heterotrimer.