Significance of Cholesterol-Binding Motifs in ABCA1, ABCG1, and SR-B1 Structure
| Autor: | L. V. Dergunova, Alexander D. Dergunov, Eugeny V. Savushkin, Dmitry Litvinov |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | The Journal of Membrane Biology. 252:41-60 |
| ISSN: | 1432-1424 0022-2631 |
| DOI: | 10.1007/s00232-018-0056-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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