Light dynamics of the retinal-disease-relevant G90D bovine rhodopsin mutant

  • 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.

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Author:Nina Kubatova, Jiafei Mao, Carl Elias Eckert, Krishna SaxenaORCiDGND, Santosh Lakshmi Gande, Josef WachtveitlORCiDGND, Clemens Glaubitz, Harald SchwalbeORCiDGND
URN:urn:nbn:de:hebis:30:3-638428
DOI:https://doi.org/10.1002/anie.202003671
ISSN:1521-3773
Parent Title (English):Angewandte Chemie
Publisher:Wiley-VCH
Place of publication:Weinheim
Document Type:Article
Language:English
Date of Publication (online):2020/06/30
Date of first Publication:2020/06/30
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/03/09
Tag:G-protein-coupled receptors; NMR spectroscopy; UV/Vis spectroscopy; retinal; rhodopsin
Volume:59
Issue:36
Page Number:8
First Page:15656
Last Page:15664
Note:
This workwas supported by the DFG (SFB807). Work at BMRZ issupported by the state of Hesse.Open access funding enabledand organized by Projekt DEAL.
Note:
A previous version of this manuscript has been published as part of a thesis (http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/52605).
HeBIS-PPN:493368183
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0