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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 α-subunit (GαCT)—stabilizes Ops*. Here we present the 3.2 Å crystal structure of the bovine Ops*–GαCT peptide complex. GαCT 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 α-helical conformation in GαCT 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*–GαCT structure and known conformational changes in Gα, we discuss signal transfer from the receptor to the G protein nucleotide-binding site.

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Figure 1: Overall structure of Ops*–GαCT complex.
Figure 2: Comparison of Ops*–GαCT and dark-state rhodopsin structures.
Figure 3: Interactions of Arg 135 of the conserved E(D)RY motif.
Figure 4: Stabilizing effects of GαCT on Ops*.
Figure 5: Conceptual model for signal transmission from the active receptor to the G protein by the Gα C terminus.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

The atomic coordinates and structure factors have been deposited in the Protein Data Bank under accession number 3DQB.


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We thank J. Engelmann and C. Koch for technical assistance; P. Henklein for peptide synthesis; C. Enenkel and M. Sommer for critically reading the manuscript; U. Müller and the scientific staff of the Protein Structure Factory and the Freie Universität Berlin at beamlines BL 14.1 and BL 14.2 at BESSY for continuous support of the project. This work was supported by the Deutsche Forschungsgemeinschaft Sfb449 (to O.P.E.), Sfb740 (to O.P.E. and K.P.H.), DFG-KOSEF international cooperation ER 294/1-1 (to O.P.E.) and F01-2004-000-10054-0 (to H.-W.C.), and CBNU funds for overseas research 2006–2007 (to H.-W.C.) and a fellowship of the Leibniz Graduate School of Molecular Biophysics, Berlin (to Y.J.K.).

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Correspondence to Hui-Woog Choe, Klaus Peter Hofmann or Oliver P. Ernst.

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Scheerer, P., Park, J., Hildebrand, P. et al. Crystal structure of opsin in its G-protein-interacting conformation. Nature 455, 497–502 (2008).

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