Activation of G-protein-coupled receptors: a common molecular mechanism.
G-protein-coupled receptors (GPCRs) are a large family of proteins that contain a seven transmembrane helical structural motif. They mediate responses to several ligands by binding and activating intracellular heterotrimeric G proteins. Since the cloning of the first GPCR, insights gained from structure-function studies, genetics and drug development have contributed to uncovering a common mechanism that explains the activation of diverse GPCRs by their cognate agonists. This mechanism takes into consideration the conservation of the structure-function relationship in the basic seven transmembrane structural motif, and the dynamic changes in receptor conformation that are associated with activation. Combining models derived from the X-ray structure of rhodopsin with structure-function data allows a deeper understanding of the activation mechanism of GPCRs.
Karnik
Sadashiva S
SS
Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. karniks@ccf.org
Gogonea
Camelia
C
Patil
Supriya
S
Saad
Yasser
Y
Takezako
Takanobu
T
D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin