title: Molecular organization and ATP-induced conformational changes of ABCA4, the photoreceptor-specific ABC transporter.
abstract: ATP-binding cassette (ABC) transporters use ATP to translocate various substrates across cellular membranes. Several members of subfamily A of mammalian ABC transporters are associated with severe health disorders, but their unusual complexity and large size have so far precluded structural characterization. ABCA4 is localized to the discs of vertebrate photoreceptor outer segments. This protein transports N-retinylidene-phosphatidylethanolamine to the outer side of disc membranes to prevent formation of toxic compounds causing macular degeneration. An 18 Å-resolution structure of ABCA4 isolated from bovine rod outer segments was determined using electron microscopy and single-particle reconstruction. Significant conformational changes in the cytoplasmic and transmembrane regions were observed upon binding of a nonhydrolyzable ATP analog and accompanied by altered hydrogen/deuterium exchange in the Walker A motif of one of the nucleotide-binding domains. These findings provide an initial view of the molecular organization and functional rearrangements for any member of the ABCA subfamily of ABC transporters.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. yxt76@case.edu
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsybovsky
authors.forename: Tivadar
authors.initials: T
authors.lastname: Orban
authors.forename: Robert S
authors.initials: RS
authors.lastname: Molday
authors.forename: Derek
authors.initials: D
authors.lastname: Taylor
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006868:Hydrolysis; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012374:Rod Cell Outer Segment / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate
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