Copyright © 2002 Krzysztof Palczewski.

Abstract

The G-protein-coupled receptor (GPCRs) superfamily comprises one of the most diverse groups of signaling molecules involved in numerous physiological processes. Binding of specific ligands to the extracellular or transmembrane domains causes conformational changes that act as a switch to relay the signal to heterotrimeric guanine nucleotide-binding proteins (G-proteins), which in turn evoke subsequent intracellular responses. More than 400 nonsensory GPCRs are also of great interest in medicine, because a vast number of therapeutic agents (>50%) are directed toward these receptors. The largest subfamily, constituting ~90% of all G-protein-coupled receptors (GPCRs), includes rhodopsins, cone pigments, and adrenergic and other receptors. Rhodopsin is involved in photon absorption in retinal rod cells and activation of transducin, a photoreceptor specific G-protein. Understanding of the conformational transformation of inactive GPCR into an activated form capable of interacting with G-protein and signal transduction is a key problem in elucidating molecular steps of cell-surface receptor signaling. The resolution of the X-ray structure of the first GPCR, rhodopsin, provides new insights on the molecular mechanism of activation[1-5].