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

Correspondence to: Klaus Peter Hofmann^1,2Hui-Woog Choe^1,3Oliver Peter Ernst¹ Correspondence and requests for materials should be addressed to O.P.E. (Email: oliver.ernst@charite.de), H.-W.C. (Email: hwchoe@chonbuk.ac.kr) or K.P.H. (Email: klaus_peter.hofmann@charite.de).

Abstract

In the G-protein-coupled receptor (GPCR) rhodopsin, the inactivating ligand 11-cis-retinal is bound in the seven-transmembrane helix (TM) bundle and is cis/trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all-trans-retinal is released, and opsin is reloaded with new 11-cis-retinal. Here we present the crystal structure of ligand-free native opsin from bovine retinal rod cells at 2.9 ångström (Å) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)_5,6F regions and in TM5–TM7. At the cytoplasmic side, TM6 is tilted outwards by 6–7 Å, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, some of which were attributed to an active GPCR state, reorganize the empty retinal-binding pocket to disclose two openings that may serve the entry and exit of retinal. The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.