Crystal structure of opsin in its G-protein-interacting conformation.
Scheerer, Patrick 1*; Park, Jung Hee 1*; Hildebrand, Peter W. 1; Kim, Yong Ju 1; Krau, Norbert 2[latin sharp s]; Choe, Hui-Woog 1,3; Hofmann, Klaus Peter 1,4; Ernst, Oliver P. 1
[Article] Nature. 455(7212):497-502, September 25, 2008.

(Format: HTML, PDF)

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 A 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)5,6F 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.

(C) 2008 Nature Publishing Group