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Light Dynamics of the Retinal‐Disease‐Relevant G90D Bovine Rhodopsin Mutant
Author(s) -
Kubatova Nina,
Mao Jiafei,
Eckert Carl Elias,
Saxena Krishna,
Gande Santosh L.,
Wachtveitl Josef,
Glaubitz Clemens,
Schwalbe Harald
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003671
Subject(s) - rhodopsin , mutant , retinal , chemistry , biophysics , population , biology , biochemistry , gene , medicine , environmental health
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.