Double Point Charge Model for Visual Pigments; Evidence From Dihydrorhodopsins*

Nakanishi, Koji; Balogh‐Nair, Valeria; Gawinowicz, Mary Ann; Arnaboldi, Maria; Motto, Michael G.; Honig, Barry

doi:10.1111/j.1751-1097.1979.tb07745.x

Cited by 27 publications

(15 citation statements)

References 10 publications

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“…These studies have provided a low resolution model for the receptor and a conceptual framework for considering specific residues in the primary structure for mutagenesis studies. Information about the structure of the retinal chromophore in rhodopsin and how it is situated with respect to the seven-helical bundle has also come from chemical, biophysical, and molecular biological approaches (16,17,19,(42)(43)(44)(45)(46)(47)(48). The salient point to emerge from these studies has been the model of a neutral chromophorebinding pocket (4, 6, 49) with significant chromophore-opsin interactions arising from amino acid residues on TM helices 3 and 6 (4 -6, 15, 50).…”

Section: Figmentioning

confidence: 99%

The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin

Han

Lin

Smith

et al. 1996

Journal of Biological Chemistry

107

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Rhodopsin is a member of a family of G protein-coupled receptors with seven transmembrane (TM) helices. In rhodopsin, Gly 121 is a highly conserved amino acid residue near the middle of TM helix 3. TM helix 3 is known to be involved in chromophore-protein interactions and contains the chromophore Schiff base counterion at position 113. We prepared a set of seven single amino acid replacement mutants of rhodopsin at position 121 (G121A, Ser, Thr, Val, Ile, Leu, and Trp) and control mutants with replacements of Gly 114 or Ala 117 . The mutant opsins were expressed in COS cells and reconstituted with either 11-cis-retinal, the groundstate chromophore of rhodopsin, or all-trans-retinal, the isomer formed upon receptor photoactivation. The replacement of Gly 121 resulted in a relative reversal in the selectivity of the opsin apoprotein for reconstitution with 11-cis-retinal over all-trans-retinal in COS cell membranes. The mutant pigments also were found to be thermally unstable to varying degrees and reactive to hydroxylamine in the dark. In addition, the size of the residue substituted at position 121 correlated directly to the degree of blue-shift in the max value of the pigment. These results suggest that Gly 121 is an important and specific component of the 11-cis-retinal binding pocket in rhodopsin.Rhodopsin, the photoreceptor molecule of the retinal rod cell, is a member of the family of G protein-coupled seven transmembrane (TM) 1 helix receptors (1). The photoreactive chromophore of rhodopsin is 11-cis-retinal, which is covalently bound in the interior of the protein as a protonated Schiff base. Photoisomerization of retinal causes receptor activation. Recently, a projection map of the TM helices has been obtained with 6-Å resolution in the plane of the membrane using electron microscopy on two-dimensional crystals of rhodopsin (2, 3). A number of biochemical and biophysical studies indicate that TM helix 3 is crucial for the activation mechanism of rhodopsin. One critical residue on TM helix 3 is Glu 113 , which serves as the counterion to the protonated retinylidene Schiff base (4 -6).Deprotonation of the Schiff base (7,8) In order to understand the mechanisms of spectral tuning and receptor photoactivation in the visual pigments, it is vital to gain additional information about the specific protein-protein and chromophore-protein contacts that define the chromophore-binding pocket in the ground state and how these contacts are affected by chromophore isomerization. There have been several models for how the retinal-protonated Schiff base interacts with Glu 113 on TM helix 3 (16 -18). In the most recent model, NMR constraints were used to position the chromophore in the interior of rhodopsin, which resulted in retinal situated between TM helices 3 and 6 with the ␤-ionone ring oriented toward TM helix 5 (19, 20). This binding site model suggests close interactions of the retinal with Gly 121 , which is strictly conserved in all visual pigments (21).We show that site-directed mutation of Gly 121 causes a de...

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Section: Figmentioning

confidence: 99%

The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin

Han

Lin

Smith

et al. 1996

Journal of Biological Chemistry

107

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“…7, 18 -30 The external point charge model was initially proposed by Honig et al to account for the opsin shift of bovine rhodopsin, in which negative charges are proposed to reside near the protonated Schiff base and in the vincinity of C-12 and C-14 of retinal. 8,9,18,31,32 The UV absorption maxima of visual pigments are regulated by subtle changes of interactions with charged and polar residues as well as water molecules through hydrogen bonding interactions. Analogously, it was proposed that a negative charged or polar residue near the β-ionone ring will stabilize the excited state relative to the ground state by enhancing electron delocalization in the π * orbital.…”

Section: Introductionmentioning

confidence: 99%

Combined QM/MM study of the opsin shift in bacteriorhodopsin

Rajamani

Gao

2001

J Comput Chem

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Combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics simulations of bacteriorhodopsin (bR) in the membrane matrix have been carried out to determine the factors that make significant contributions to the opsin shift. We found that both solvation and interactions with the protein significantly shifts the absorption maximum of the retinal protonated Schiff base, but the effects are much more pronounced in polar solvents such as methanol, acetonitrile, and water than in the protein environment. The differential solvatochromic shifts of PSB in methanol and in bR leads to a bathochromic shift of about 1800 cm(-1). Because the combined QM/MM configuration interaction calculation is essentially a point charge model, this contribution is attributed to the extended point-charge model of Honig and Nakanishi. The incorporation of retinal in bR is accompanied by a change in retinal conformation from the 6-s-cis form in solution to the 6-s-trans configuration in bR. The extension of the pi-conjugated system further increases the red-shift by 2400 cm(-1). The remaining factors are due to the change in dispersion interactions. Using an estimate of about 1000 cm(-1) in the dispersion contribution by Houjou et al., we obtained a theoretical opsin shift of 5200 cm(-1) in bR, which is in excellent agreement with the experimental value of 5100 cm(-1). Structural analysis of the PSB binding site revealed the specific interactions that make contributions to the observed opsin shift. The combined QM/MM method used in the present study provides an opportunity to accurately model the photoisomerization and proton transfer reactions in bR.

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“…Blue shifts of the absorbance maxima could be attributed to deprotonation of the counter-anion of the Schiff-base (probably a carboxyl group, Nakanishi et al 1979, Honig andEbrey 1982). Since the blue shift only occurs in the presence of K + there could be a competition between protons and potassium ions introduced in the vicinity of the retinal by valinomycin.…”

Section: Discussionmentioning

confidence: 99%

Light adaptation of bacteriorhodopsin in the presence of valinomycin and potassium. pH-dependence

1988

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In the presence of valinomycin and K(+), bacteriorhodopsin undergoes (i) a decrease of its maximum absorbance, (ii) a blue shift of the maximum wavelength of both the light and the dark adapted forms. However (iii) a normal light adaptation is maintained and (iv) the retinal-retinal interactions are not perturbed. The role of valinomycin as a K(+)-carrier allowing a H(+)-K(+) competition as well as the stabilization of the deprotonated Schiff-base (linking retinal to the apo-opsin) is shown and discussed.

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Double Point Charge Model for Visual Pigments; Evidence From Dihydrorhodopsins*

Cited by 27 publications

References 10 publications

The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin

The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin

Combined QM/MM study of the opsin shift in bacteriorhodopsin

Light adaptation of bacteriorhodopsin in the presence of valinomycin and potassium. pH-dependence

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