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Light Dynamics of the Retinal‐Disease‐Relevant G90D Bovine Rhodopsin Mutant
- Source :
- Angewandte Chemie (International Ed. in English)
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- The RHO gene encodes the G‐protein‐coupled receptor (GPCR) rhodopsin. Numerous mutations associated with impaired visual cycle have been reported; the G90D mutation leads to a constitutively active mutant form of rhodopsin that causes CSNB disease. We report on the structural investigation of the retinal configuration and conformation in the binding pocket in the dark and light‐activated state by solution and MAS‐NMR spectroscopy. We found two long‐lived dark states for the G90D mutant with the 11‐cis retinal bound as Schiff base in both populations. The second minor population in the dark state is attributed to a slight shift in conformation of the covalently bound 11‐cis retinal caused by the mutation‐induced distortion on the salt bridge formation in the binding pocket. Time‐resolved UV/Vis spectroscopy was used to monitor the functional dynamics of the G90D mutant rhodopsin for all relevant time scales of the photocycle. The G90D mutant retains its conformational heterogeneity during the photocycle.<br />Rhodopsin is the major dim light receptor in vertebrate eyes. Numerous mutations associated with impaired visual cycles are known. The G90D mutation leads to a constitutively active mutant form of rhodopsin that causes congenital stationary night blindness (CSNB). We investigated the consequences of this mutation on the visual cycle, both in terms of structural aspects and dynamic changes.
- Subjects :
- Models, Molecular
Protein Folding
Light
genetic structures
Protein Conformation
Mutant
Population
G-protein-coupled receptors
010402 general chemistry
medicine.disease_cause
retinal
01 natural sciences
Catalysis
G‐Protein‐Coupled Receptors | Hot Paper
chemistry.chemical_compound
NMR spectroscopy
Retinal Diseases
medicine
Animals
UV/Vis spectroscopy
education
Research Articles
G protein-coupled receptor
Mutation
education.field_of_study
biology
010405 organic chemistry
Chemistry
Retinal
General Medicine
General Chemistry
0104 chemical sciences
rhodopsin
Rhodopsin
biology.protein
Biophysics
Cattle
Salt bridge
Research Article
Visual phototransduction
Subjects
Details
- ISSN :
- 15213773 and 14337851
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition
- Accession number :
- edsair.doi.dedup.....8706e5a13d3cd7cd9f3d87c45ec5d4da