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.