ArticleThe Journal of biological chemistry2010
Interaction of extracellular domain 2 of the human retina-specific ATP-binding cassette transporter (ABCA4) with all-trans-retinal.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- In Silico Prioritization of Variants of Uncertain Significance in ABCA4 Reveals Conserved Functional Motifs.Research square · 2026Article
- Lipid transport mechanisms in human ABCA family transporters: a structural perspective.Biochemical Society transactions · 2026Review
- Stargardt's Disease: Molecular Pathogenesis and Current Therapeutic Landscape.International journal of molecular sciences · 2025Review
- Assessment of ABCA4 Genetic Variants: Current Landscape and Future Prospects.Advances in experimental medicine and biology · 2025Review
- Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.Advances in protein chemistry and structural biology · 2025Review
- Exploring the Role of ABCA4's ECD2 Domain in Inherited Retinal Degeneration: Computational and Functional Perspectives.Advances in experimental medicine and biology · 2025Article
- Structural and Pathogenic Impacts ofInternational journal of molecular sciences · 2023Article
- Protein modeling and in silico analysis to assess pathogenicity ofMolecular vision · 2023Article
- Structural basis of substrate recognition and translocation by human ABCA4.Nature communications · 2021Article
- Article
- Expression, purification and structural properties of ABC transporter ABCA4 and its individual domains.Protein expression and purification · 2014Article
- Molecular organization and ATP-induced conformational changes of ABCA4, the photoreceptor-specific ABC transporter.Structure (London, England : 1993) · 2013Article
- Retinoid binding properties of nucleotide binding domain 1 of the Stargardt disease-associated ATP binding cassette (ABC) transporter, ABCA4.The Journal of biological chemistry · 2012Article
- ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer.Nature communications · 2012Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The retina-specific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal from the rod outer segment discs in the retina and is associated with a broad range of inherited retinal diseases, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. A unique feature of the ABCA subfamily of ABC transporters is the presence of highly conserved, long extracellular loops or domains (ECDs) with unknown function. The high degree of sequence conservation and mapped disease-associated mutations in these domains suggests an important physiological significance. Conformational analysis using CD spectroscopy of purified, recombinant ECD2 protein demonstrated that it has an ordered and stable structure composed of 27 +/- 3% alpha-helix, 20 +/- 3% beta-pleated sheet, and 53 +/- 3% coil. Significant conformational changes were observed in disease-associated mutant proteins. Using intrinsic tryptophan fluorescence emission spectrum of ECD2 polypeptide and fluorescence anisotropy, we have demonstrated that this domain specifically interacts with all-trans-retinal. Furthermore, the retinal interaction appeared preferential for the all-trans-isomer and was directly measurable through fluorescence anisotropy analysis. Our results demonstrate that the three macular degeneration-associated mutations lead to significant changes in the secondary structure of the ECD2 domain of ABCA4, as well as in its interaction with all-trans-retinal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.