Crystal structure of opsin in its G-protein-interacting conformation

Opsin, the ligand- free form of the G- protein- coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G- protein- binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein - the carboxy terminus of the alpha-subunit (G alpha CT) - stabilizes Ops*. Here we present the 3.2 angstrom crystal structure of the bovine Ops* - G alpha CT peptide complex. G alpha CT binds to a site in opsin that is opened by an outward tilt of transmembrane helix ( TM) 6, a pairing of TM5 and TM6, and a restructured TM7 - helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha- helical conformation in G alpha CT with a C- terminal reverse turn. Main- chain carbonyl groups in the reverse turn constitute the centre of a hydrogen- bonded network, which links the two receptor regions containing the conserved E( D) RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops* - G alpha CT structure and known conformational changes in G alpha, we discuss signal transfer from the receptor to the G protein nucleotide- binding site.