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Tytuł pozycji:

Effect of Sodium Valproate on the Conformational Stability of the Visual G Protein-Coupled Receptor Rhodopsin

Tytuł:
Effect of Sodium Valproate on the Conformational Stability of the Visual G Protein-Coupled Receptor Rhodopsin
Autorzy:
Neda Razzaghi
Pol Fernandez-Gonzalez
Aina Mas-Sanchez
Guillem Vila-Julià
Juan Jesus Perez
Pere Garriga
Temat:
rhodopsin
G protein-coupled receptor
sodium valproate
retinitis pigmentosa
conformational stability
Organic chemistry
QD241-441
Źródło:
Molecules, Vol 26, Iss 10, p 3032 (2021)
Wydawca:
MDPI AG, 2021.
Rok publikacji:
2021
Kolekcja:
LCC:Organic chemistry
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1420-3049
Relacje:
https://www.mdpi.com/1420-3049/26/10/3032; https://doaj.org/toc/1420-3049
DOI:
10.3390/molecules26103032
Dostęp URL:
https://doaj.org/article/62ee022c99b547fea591167445101a0c  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.62ee022c99b547fea591167445101a0c
Czasopismo naukowe
Rhodopsin is the G protein-coupled receptor of rod photoreceptor cells that mediates vertebrate vision at low light intensities. Mutations in rhodopsin cause inherited retinal degenerative diseases such as retinitis pigmentosa. Several therapeutic strategies have attempted to address and counteract the deleterious effect of rhodopsin mutations on the conformation and function of this photoreceptor protein, but none has been successful in efficiently preventing retinal degeneration in humans. These approaches include, among others, the use of small molecules, known as pharmacological chaperones, that bind to the receptor stabilizing its proper folded conformation. Valproic acid, in its sodium valproate form, has been used as an anticonvulsant in epileptic patients and in the treatment of several psychiatric disorders. More recently, this compound has been tested as a potential therapeutic agent for the treatment of retinal degeneration associated with retinitis pigmentosa caused by rhodopsin mutations. We now report on the effect of sodium valproate on the conformational stability of heterologously expressed wild-type rhodopsin and a rhodopsin mutant, I307N, which has been shown to be an appropriate model for studying retinal degeneration in mice. We found no sign of enhanced stability for the dark inactive conformation of the I307N mutant. Furthermore, the photoactivated conformation of the mutant appears to be destabilized by sodium valproate as indicated by a faster decay of its active conformation. Therefore, our results support a destabilizing effect of sodium valproate on rhodopsin I307N mutant associated with retinal degeneration. These findings, at the molecular level, agree with recent clinical studies reporting negative effects of sodium valproate on the visual function of retinitis pigmentosa patients.

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