First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation
| العنوان: | First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation |
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| المؤلفون: | Valentin Gogonea, Kailash Gulshan, Gregory Brubaker, Jonathan D. Smith, Shuhui Wang Lorkowski, Stanley L. Hazen |
| المصدر: | PLoS ONE PLoS ONE, Vol 15, Iss 1, p e0221915 (2020) |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Circular dichroism, Apolipoprotein B, Lipid-anchored protein, Plasma protein binding, Crystallography, X-Ray, 01 natural sciences, Guanidines, Biochemistry, Protein Structure, Secondary, Mice, chemistry.chemical_compound, Protein structure, Post-Translational Modification, Site-directed mutagenesis, Guanidine, Sequence Deletion, 0303 health sciences, Liposome, Crystallography, Multidisciplinary, biology, Chemistry, Physics, Circular Dichroism, Condensed Matter Physics, Lipids, Cholesterol, Physical Sciences, Crystal Structure, Medicine, Disulfide Bonds, lipids (amino acids, peptides, and proteins), Cellular Structures and Organelles, Research Article, ATP Binding Cassette Transporter 1, Protein Binding, Science, 010402 general chemistry, 03 medical and health sciences, Lipid Structure, Genetics, Solid State Physics, Point Mutation, Animals, Humans, Vesicles, 030304 developmental biology, Protein Unfolding, Apolipoprotein A-I, 030102 biochemistry & molecular biology, Point mutation, C-terminus, Chemical Compounds, Biology and Life Sciences, Proteins, Biological Transport, Cell Biology, Lipid Metabolism, 0104 chemical sciences, Kinetics, RAW 264.7 Cells, 030104 developmental biology, Bundle, Liposomes, Mutation, biology.protein, Mutagenesis, Site-Directed, Biophysics, ATP-Binding Cassette Transporters |
| الوصف: | The crystal structure of a C-terminal deletion of apolipoprotein A-I (apoA1) shows a large helical bundle structure in the amino half of the protein, from residues 8 to 115. Using site directed mutagenesis, guanidine or thermal denaturation, cell free liposome clearance, and cellular ABCA1-mediated cholesterol efflux assays, we demonstrate that apoA1 lipidation can occur when the barrier to this bundle unfolding is lowered. The absence of the C-terminus renders the bundle harder to unfold resulting in loss of apoA1 lipidation that can be reversed by point mutations, such as Trp8Ala, and by truncations as short as 8 residues in the amino terminus, both of which lower the barrier to helical bundle unfolding. Locking the bundle via a disulfide bond leads to loss of apoA1 lipidation. We propose a model in which the C-terminus acts on the N-terminus to destabilize helical bundle. Upon lipid binding to the C-terminus, Trp8 is displaced from its interaction with Phe57, Arg61, Leu64, Val67, Phe71, and Trp72 to destabilize the bundle. However, when the C-terminus is deleted, Trp8 cannot be displaced, the bundle cannot unfold, and apoA1 cannot be lipidated. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5284444a20aa7a073e3937d57ac98b38Test https://doi.org/10.1371/journal.pone.0221915Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5284444a20aa7a073e3937d57ac98b38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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