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Esther E. Biswas-Fiss, Malissa Ha, Deepa Kurpad, Subhasis B. Biswas; Retinoid Binding Properties of the Nucleotide Binding Domains of Human ABCA4 Protein. Invest. Ophthalmol. Vis. Sci. 2011;52(14):51.
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The retina-specific ABC transporter, ABCA4, is essential for the recycling of 11-cis-retinal utilized by opsin as part of the visual transduction cycle. Mutations in the ABCA4 gene are associated with a broad range of inherited macular degenerations including Stargardt disease (STGD), autosomal recessive cone rod dystrophy (arCRD) and fundus flavimaculatus (FFM). Previously we have described the retinal binding activity of the second extracellular domain (ECD2) of human ABCA4 protein (Biswas-Fiss, E. E. et al. (2010) J Biol Chem. 285(25):19372-83). In this study the retinoid binding properties of the nucleotide binding domains (NBDs) of ABCA4 transporter were investigated.
Using recombinant polypeptides derived from the amino acid sequences of NBD1and NBD2 domains, we have determined the interaction affinities of retinoid binding to these two domains of ABCA4.
Fluorescence anisotropy and tryptophan emission spectroscopy demonstrated considerable differences in affinities between these two domains.
These results support the hypothesis that the nucleotide domains of ABCA4 may play further roles in protein function in addition to that of nucleotide hydrolysis; furthermore Stargardt disease associated mutations may lead to significant changes in the retinoid binding affinity of these domains.
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