Significance of Cholesterol-Binding Motifs in ABCA1, ABCG1, and SR-B1 Structure
| العنوان: | Significance of Cholesterol-Binding Motifs in ABCA1, ABCG1, and SR-B1 Structure |
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| المؤلفون: | L. V. Dergunova, Alexander D. Dergunov, Eugeny V. Savushkin, Dmitry Litvinov |
| المصدر: | The Journal of Membrane Biology. 252:41-60 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | CD36 Antigens, Models, Molecular, Physiology, 030310 physiology, In silico, Amino Acid Motifs, Molecular Conformation, Biophysics, Structure-Activity Relationship, 03 medical and health sciences, Molecular recognition, Protein structure, polycyclic compounds, Inner membrane, Protein Interaction Domains and Motifs, Amino Acid Sequence, ATP Binding Cassette Transporter, Subfamily G, Member 1, 030304 developmental biology, 0303 health sciences, Binding Sites, biology, Chemistry, Cholesterol binding, Cell Biology, Transmembrane protein, Cholesterol, ABCA1, biology.protein, lipids (amino acids, peptides, and proteins), Efflux, ATP Binding Cassette Transporter 1, Protein Binding |
| الوصف: | 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. |
| تدمد: | 1432-1424 0022-2631 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eec219a637833f603d4e0566c5baddec https://doi.org/10.1007/s00232-018-0056-5 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....eec219a637833f603d4e0566c5baddec |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14321424 00222631 |
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