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

摘要

Opsin, the ligand-f ree form of the G-protein-coupled receptor rhodopsin, at low phi adopts a conformatlonally distinct, active G-protein-binding state known as Ops~*. A synthetic peptide derived from the main binding site of the heterotrtmeric G protein-the carboxy terminus of the α-subunit (GaCT)-stabilizes Ops~*. Here we present the 3.2 A crystal structure of the bovine Ops~*-GαCT peptide complex. GaCT 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 a-helical conformation in GaCT 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~*-GαCT structure and known conformational changes in Got, we discuss signal transfer from the receptor to the G protein nucleotide-binding site.