Disruption of Hydrogen-Bond Network in Rhodopsin Mutations Cause Night Blindness
| Autor: | Hideki Kandori, Yuri Takeyama, Akiko Enomoto, Kota Katayama, Hiroo Imai |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Opsin Rhodopsin genetic structures Protein Conformation Mutant 03 medical and health sciences 0302 clinical medicine Photosensitivity Isomerism Structural Biology Night Blindness Animals Point Mutation Molecular Biology 030304 developmental biology 0303 health sciences biology Hydrogen bond Chemistry Regeneration (biology) Hydrogen Bonding Chromophore biology.protein Biophysics Retinaldehyde Cattle sense organs Isomerization 030217 neurology & neurosurgery |
| Zdroj: | Journal of molecular biology. 432(19) |
| ISSN: | 1089-8638 |
| Popis: | Rhodopsin is the photosensitive protein, which binds to 11-cis-retinal as its chromophore. In the dark, rhodopsin exists as a stable complex between the opsin moiety and 11-cis-retinal. The absorption of a light photon converts 11-cis-retinal to all-trans-retinal and initiates our vision. As a result, the increase in the rate of dark activation of rhodopsin reduces its photosensitivity resulting in night blindness. The mutations, G90D and T94I are night blindness-causing mutations that exhibit completely different physicochemical characteristics associated with the dark activation of rhodopsin, such as a high rate of thermal isomerization of 11-cis-retinal and a slow pigment regeneration. To elucidate the molecular mechanism by which G90D and T94I mutations affect rhodopsin dark activation and regeneration, we performed light-induced difference FTIR spectroscopy on dark and primary photo-intermediate states of G90D and T94I mutants. The FTIR spectra clearly show that both charged G90D and hydrophobic T94I mutants alter the H-bond network at the Schiff base region of the chromophore, which weakens the electrostatic interaction with Glu113 counterion. Our results further show an altered water-mediated H-bond network around the central transmembrane region of mutant rhodopsin, which is reminiscent of the active Meta-II state. This altered water-mediated H-bond network may cause thermal isomerization of the chromophore and facilitate rhodopsin dark activation. |
| Databáze: | OpenAIRE |
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