Visual signals in retinal rod cells are triggered by the interaction of the photoexcited rhodopsin phho with the heterotrimeric GTP-binding protein transducin (Gt). The GTP-bound form of activated Gt differs markedly from the inactive GDP bound state. Molecular details of the mechanism by which Rh catalyzes the nucleotide exchange remain obscure. Several protein domains on the alpha and beta-gamma-subunits of Gt contribute to the rhodopsin binding site on the G protein. An eleven-residue segment at the carboxyl terminus of the alpha-subunit, Gtalpha(340-350), has been shown to play a major role in receptor recognition and nucleotide exchange. We report the structure of the Gtalpha(340-350) peptide bound to the photoexcited rhodopsin obtained by TRNOE spectroscopy. Light-induced changes in rhodopsin cause a dramatic shift in the conformation of the undecapeptide. Utilizing the crystal structure of Gt in which Gtalpha(344-350) is disordered one can overlap the last four residues visible by crystallography with the first four residues on the NMR structure to visualize the impact of the activated receptor on transducin. Gtalpha(340-350) points away from Gt in the direction where rhodopsin is expected to be found in the ternary complex based on mutational studies. The light-induced rearrangement in the Gtalpha(340-350) suggests a mechanism of the receptor-catalyzed G-protein activation.
|State||Published - Dec 1 1997|