Year: 2015
Type: article
Abstract: Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate the aggregation of misfolded opsin mutants. The effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.
Source: FEBS Letters
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Energy, Research to Prevent Blindness, Case Western Reserve University, Universiteit van Amsterdam, National Institutes of Health, Office of Science, National Eye Institute, National Center for Research Resources, Basic Energy Sciences, Office of Research Infrastructure Programs, National Institutes of Health
Awards: G1126863173, G1286236842, G1286251239, G1540503468, G1847291448, G196819017, G241279073, G30714459, G3083819904, G338944111, G357145406, G382641700, G4132518751, G4183155088, G419881185, G42916606, G4501827968, G498139845, G5094664921, G5292656900, G549834383, G5765906131, G650090426, Synchrotron-Based Infrared Microscope for Chemical Imaging of Disease, G6965541988, Acquisition of a Leica TCS SP5 Confocal Microscope For A Multi-User Facility, G7463374569, G8507651203, G8883367568, G9000003055, G9000162321, G9000177402, G969889393
OpenAlex ID: W1947050232