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A Phe‐rich region in short‐wavelength sensitive opsins is responsible for their aggregation in the absence of 11‐ cis‐ retinal
Author(s) -
Zhang Tao,
Fu Yingbin
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.06.012
Subject(s) - opsin , retinal , wavelength , biophysics , chemistry , retinaldehyde , photochemistry , rhodopsin , biology , physics , optics , biochemistry
Human blue and mouse S‐opsin are prone to aggregation in the absence of 11‐cis‐retinal, which underlie the rapid cone degeneration in human patients and animal models of Leber congenital amaurosis (LCA). By in silico analysis and domain swapping experiments, we show that a Phe‐rich region in short‐wavelength sensitive (SWS) opsins, but not in medium/long‐wavelength sensitive opsins, is responsible for SWS opsin aggregation. Mutagenesis studies suggest that Phe residues in this region are critical in mediating protein aggregation. Fusing the Phe‐rich region of SWS opsins to GFP causes the latter to aggregate. Our findings suggest that new therapeutics can be designed to disrupt the Phe‐rich region in preventing cone degeneration due to S‐opsin aggregation in LCA.