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. 2006 Aug 22;103(34):12729-34.
doi: 10.1073/pnas.0601765103. Epub 2006 Aug 14.

Local peptide movement in the photoreaction intermediate of rhodopsin

Hitoshi Nakamichi  1 , Tetsuji Okada
Affiliations

Affiliation

  • 1 Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.

Local peptide movement in the photoreaction intermediate of rhodopsin

Hitoshi Nakamichi et al. Proc Natl Acad Sci U S A. .
. 2006 Aug 22;103(34):12729-34.
doi: 10.1073/pnas.0601765103. Epub 2006 Aug 14.

Authors

Hitoshi Nakamichi  1 , Tetsuji Okada

Affiliation

  • 1 Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.

Abstract

Photoactivation of the visual rhodopsin, a prototypical G protein-coupled receptor (GPCR), involves efficient conversion of the intrinsic inverse-agonist 11-cis-retinal to the all-trans agonist. This event leads to the rearrangement of the heptahelical transmembrane bundle, which is thought to be shared by hundreds of GPCRs. To examine this activation mechanism, we determined the x-ray crystallographic model of the photoreaction intermediate of rhodopsin, lumirhodopsin, which represents the conformational state having the nearly complete all-trans agonist form of the retinal. A difference electron density map clearly indicated that the distorted all-trans-retinal in the precedent intermediate bathorhodopsin relaxes by dislocation of the beta-ionone ring in lumirhodopsin, along with significant peptide displacement in the middle of helix III, including approximately two helical turns. This local movement results in the breaking of the electrostatic interhelical restraints mediated by many of the conserved residues among rhodopsin-like GPCRs, with consequent acquisition of full activity.

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Conflict of interest statement

Conflict of interest statement: No conflicts declared.

Figures

Fig. 1.

Fig. 1.

Conversion from RHO to LUMI…

Fig. 1.

Conversion from RHO to LUMI in a 3D crystal. ( A ) Difference…

Fig. 1.
Conversion from RHO to LUMI in a 3D crystal. (A) Difference electron densities calculated from x-ray diffraction data at 160 K. Three purple double arrows indicate the slab sections shown in Fig. 3 A–C. (B) Spectral changes observed upon conversion from RHO to BATHO (100 K) and to LUMI (130 K, 140 K) in a 3D crystal. These spectra were obtained after subtraction of the ground-state spectrum. (C) Expanded view of the difference electron densities around the retinal. In A and C, positive and negative electron densities are shown in blue and red, respectively, on the ground-state α-carbon polypeptide chain of RHO. The maps are contoured to 3.5σ level for one of the two molecules in the crystallographic asymmetric unit. The chromophores (11-cis-retinal + Lys-296) of RHO and LUMI are in green and orange, respectively. Figs. 1 and 3 were prepared with SPDBV (15).
Fig. 2.

Fig. 2.

Structural changes of the retinal…

Fig. 2.

Structural changes of the retinal chromophore after photoexcitation of the RHO crystal. ( …

Fig. 2.
Structural changes of the retinal chromophore after photoexcitation of the RHO crystal. (A and B) Conversion from RHO (green) to BATHO (red) is derived from ref. . (C and D) Conversion from BATHO (red) to LUMI (orange). B and D are different views from A and C, respectively, rotated ≈90° around the horizontal axis. Nitrogen atoms are in blue. Figs. 2 and 4 were prepared with MolScript (21) and Raster3D (22).
Fig. 3.

Fig. 3.

Differences between RHO and LUMI.…

Fig. 3.

Differences between RHO and LUMI. ( A – C ) Projection views of…

Fig. 3.
Differences between RHO and LUMI. (A–C) Projection views of the three regions containing the difference electron densities between RHO and LUMI. Each image is a 10-Å slab section from the extracellular (A) to cytoplasmic (C) side of the transmembrane helical domain. Positive (blue) and negative (red) electron densities contoured to 3.5σ level are shown on the α-carbon traces of the seven helices. (D) Superposition of the crystallographic models of RHO (green) and LUMI (orange). Only the α-carbon traces and the retinal chromophore are shown.
Fig. 4.

Fig. 4.

Crystallographic models of the three…

Fig. 4.

Crystallographic models of the three states of RHO. ( A ) Projection view…

Fig. 4.
Crystallographic models of the three states of RHO. (A) Projection view around the retinal with some amino acid residues. Shown are the three models: RHO (green), BATHO (red), and LUMI (orange). (B) Structural changes between RHO (green) and LUMI (orange) around the middle of helix III. The four bound water molecules in this site are shown as small light blue spheres, which are fixed in the positions found in the ground-state structure.
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