Park Paul S-H, Lodowski David T, Palczewski Krzysztof
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4965, USA.
Annu Rev Pharmacol Toxicol. 2008;48:107-41. doi: 10.1146/annurev.pharmtox.48.113006.094630.
Transformation of G protein-coupled receptors (GPCRs) from a quiescent to an active state initiates signal transduction. All GPCRs share a common architecture comprising seven transmembrane-spanning alpha-helices, which accommodates signal propagation from a diverse repertoire of external stimuli across biological membranes to a heterotrimeric G protein. Signal propagation through the transmembrane helices likely involves mechanistic features common to all GPCRs. The structure of the light receptor rhodopsin may serve as a prototype for the transmembrane architecture of GPCRs. Early biochemical, biophysical, and pharmacological studies led to the conceptualization of receptor activation based on the context of two-state equilibrium models and conformational changes in protein structure. More recent studies indicate a need to move beyond these classical paradigms and to consider additional aspects of the molecular character of GPCRs, such as the oligomerization and dynamics of the receptor.
G蛋白偶联受体（GPCRs）从静止状态转变为激活状态会启动信号转导。所有GPCRs都具有共同的结构，包括七个跨膜α螺旋，它能够将来自各种外部刺激的信号穿过生物膜传递给异源三聚体G蛋白。通过跨膜螺旋的信号传递可能涉及所有GPCRs共有的机制特征。光受体视紫红质的结构可作为GPCRs跨膜结构的原型。早期的生化、生物物理和药理学研究基于双态平衡模型和蛋白质结构的构象变化，形成了受体激活的概念。最近的研究表明，需要超越这些经典范式，考虑GPCRs分子特性的其他方面，如受体的寡聚化和动力学。
