Ciarkowski J, Drabik P, Giełdoń A, Kaźmierkiewicz R, Slusarz R
Faculty of Chemistry, University of Gdańsk, Poland.
Acta Biochim Pol. 2001;48(4):1203-7.
G protein-coupled receptors (GPCRs) transducing diverse external signals to cells via activation of heterotrimeric GTP-binding (G) proteins, estimated to mediate actions of 60% of drugs, had been resistant to structure determination until summer 2000. The first atomic-resolution experimental structure of a GPCR, that of dark (inactive) rhodopsin, thus provides a trustworthy 3D prototype for antagonist-bound forms of this huge family of proteins. In this work, our former theoretical GPCR models are evaluated against the new experimental template. Subsequently, a working hypothesis regarding the signal transduction mechanism by GPCRs is presented.
G蛋白偶联受体（GPCRs）通过激活异源三聚体GTP结合蛋白（G蛋白）将多种外部信号传导至细胞，据估计，60%的药物作用都由其介导。直到2000年夏天，GPCRs一直难以确定其结构。GPCR的第一个原子分辨率实验结构，即暗（无活性）视紫红质的结构，因此为该庞大蛋白质家族的拮抗剂结合形式提供了一个可靠的三维原型。在这项工作中，我们以前的理论GPCR模型与新的实验模板进行了评估。随后，提出了一个关于GPCR信号转导机制的工作假设。
