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Significance of Cholesterol-Binding Motifs in ABCA1, ABCG1, and SR-B1 Structureстатья
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 11 мая 2021 г.
- Авторы: Dergunov Alexander D., Savushkin Eugeny V., Dergunova Liudmila V., Litvinov Dmitry Y.
- Журнал: Journal of Membrane Biology
- Том: 252
- Номер: 1
- Год издания: 2018
- Издательство: Springer Verlag
- Местоположение издательства: Germany
- Первая страница: 41
- Последняя страница: 60
- DOI: 10.1007/s00232-018-0056-5
- Аннотация: ABCA1, ABCG1 transporters, and SR-B1 receptor are the major proteins involved in cholesterol efflux from cells. We superposed in silico the location of putative cholesterol (Chol)-binding motifs CRAC/CARC and CCM in human ABCA1, ABCG1, and SR-B1 with (1) transmembrane protein topology, (2) a profile of structural order of protein, and (3) with an influence of single amino acid substitutions on protein structure and function. ABCA1, ABCG1, and SR-B1 molecules contain 50, 19, and 13 Chol-binding motifs, respectively, that are localized either in membrane helices, or at membrane-water interface, or in water-exposed protein regions. Arginine residues in motifs that coincide with molecular recognition features within intrinsically disordered regions of the transporters are suggested to be important in cholesterol binding; cholesterol-arginine interaction may result in the induction of local order in protein structure. Chol-binding motifs in membrane helices may immobilize cholesterol, while motifs at membrane-water interface may be involved into the efflux of "active" cholesterol. Cholesterol may interfere with ATP binding in both nucleotide-binding domains of ABCA1 structure. For ABCA1 and ABCG1, but not for SR-B1, the presence of mirror code as a CARC-CRAC vector couple in the C-terminal helices controlling protein-cholesterol interactions in the outer and inner membrane leaflets was evidenced. We propose the role of Chol-binding motifs with different immersion in membrane in transport of different cholesterol pools by ABCA1 and ABCG1.
- Добавил в систему: Савушкин Евгений Владимирович