1. Institut für Medizinische Physik und Biophysik (CC2), Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany
2. Queen Mary, University of London, School of Biological and Chemical Sciences, London E1 4NS, UK
3. Department of Chemistry, College of Natural Science, Chonbuk National University, 561-756 Chonju, South Korea
4. Zentrum für Biophysik und Bioinformatik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin, Germany
5. These authors contributed equally to this work.

Correspondence to: Hui-Woog Choe^1,3Klaus Peter Hofmann^1,4Oliver P. Ernst¹ Correspondence and requests for materials should be addressed to O.P.E. (Email: oliver.ernst@charite.de), K.P.H. (Email: klaus_peter.hofmann@charite.de) or H.-W.C. (Email: hwchoe@chonbuk.ac.kr).

Abstract

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

1. Institut für Medizinische Physik und Biophysik (CC2), Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany
2. Queen Mary, University of London, School of Biological and Chemical Sciences, London E1 4NS, UK
3. Department of Chemistry, College of Natural Science, Chonbuk National University, 561-756 Chonju, South Korea
4. Zentrum für Biophysik und Bioinformatik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin, Germany
5. These authors contributed equally to this work.

Correspondence to: Hui-Woog Choe^1,3Klaus Peter Hofmann^1,4Oliver P. Ernst¹ Correspondence and requests for materials should be addressed to O.P.E. (Email: oliver.ernst@charite.de), K.P.H. (Email: klaus_peter.hofmann@charite.de) or H.-W.C. (Email: hwchoe@chonbuk.ac.kr).

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