Signal transmission via G protein-coupled receptors in the light of rhodopsin structure determination.
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.
Ciarkowski
J
J
Faculty of Chemistry, University of Gdańsk, Poland. jurek@chemik.chem.univ.gda.pl
Drabik
P
P
Giełdoń
A
A
Kaźmierkiewicz
R
R
Slusarz
R
R
D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000737:chemistry*; D017483:Receptors, Vasopressin / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry*; D015398:Signal Transduction
D008024:Ligands; D011956:Receptors, Cell Surface; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D012243:Rhodopsin