X-ray crystallographic studies for ligand-protein interaction changes in rhodopsin.

G-protein-coupled receptors constitute the largest transmembrane receptor family in human. They are generally activated on binding their specific ligands at the extracellular side of membranes. The signal carried by an agonist is then transmitted to the intracellular side through a conformational change of the receptor, which becomes competent to catalyse GDP/GTP exchange in the alpha-subunit of heterotrimeric G-protein. Since most of the G-protein-coupled receptors (rhodopsin-like subfamily) share a set of conserved amino acid residues in the transmembrane domain, it is probable that the ligand-triggered activation process involves a common mechanism of rearrangement of the hepta-helical transmembrane bundle. For understanding the nature of this event that is not yet characterized sufficiently, X-ray crystallographic studies of rhodopsin with or without light stimulation can provide valuable information. In rhodopsin, the initial cis-trans photoisomerization of retinal chromophore triggers the structural changes of transmembrane helices. This activation process has been characterized with some spectroscopically distinct photoreaction intermediates (batho, lumi, Meta I and Meta II). With recent advances in the conditions for crystallographic experiments, the diffraction limit of the rhodopsin crystals has been substantially extended. As a result, it becomes possible to detect small structural changes evoked after photoactivation under cryogenic conditions.