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Location of the Retinal Chromophore in the Activated State of Rhodopsin

Ahuja, Shivani and Crocker, Evan and Eilers, Markus and Hornak, Viktor and Hirshfeld, Amiram and Ziliox, Martine and Syrett, Natalie and Reeves, Philip J and Khorana, H Gobind and Sheves, Mordechai and Smith, Steven O (2009) 'Location of the Retinal Chromophore in the Activated State of Rhodopsin.' Journal of Biological Chemistry, 284 (15). pp. 10190-10201. ISSN 0021-9258

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Abstract

Rhodopsin is a highly specialized G protein-coupled receptor (GPCR) that is activated by the rapid photochemical isomerization of its covalently bound 11-cis-retinal chromophore. Using two-dimensional solid-state NMR spectroscopy, we defined the position of the retinal in the active metarhodopsin II intermediate. Distance constraints were obtained between amino acids in the retinal binding site and specific 13C-labeled sites located on the β-ionone ring, polyene chain, and Schiff base end of the retinal. We show that the retinal C20 methyl group rotates toward the second extracellular loop (EL2), which forms a cap on the retinal binding site in the inactive receptor. Despite the trajectory of the methyl group, we observed an increase in the C20-Gly188 (EL2) distance consistent with an increase in separation between the retinal and EL2 upon activation. NMR distance constraints showed that the β-ionone ring moves to a position between Met207 and Phe208 on transmembrane helix H5. Movement of the ring toward H5 was also reflected in increased separation between the C∈ carbons of Lys296 (H7) and Met44 (H1) and between Gly121 (H3) and the retinal C18 methyl group. Helix-helix interactions involving the H3-H5 and H4-H5 interfaces were also found to change in the formation of metarhodopsin II reflecting increased retinal-protein interactions in the region of Glu122 (H3) and His211 (H5). We discuss the location of the retinal in metarhodopsin II and its interaction with sequence motifs, which are highly conserved across the pharmaceutically important class A GPCR family, with respect to the mechanism of receptor activation. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Item Type: Article
Uncontrolled Keywords: Retina; Cell Line; Humans; Polyenes; Schiff Bases; Rhodopsin; Receptors, G-Protein-Coupled; Magnetic Resonance Spectroscopy; Binding Sites; Molecular Conformation; Protein Conformation; Rod Cell Outer Segment
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 07 Oct 2011 14:10
Last Modified: 15 Jan 2022 00:35
URI: http://repository.essex.ac.uk/id/eprint/929

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