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Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new useful target for hypercholesterolemia treatment. This work demonstrates that natural peptides, deriving from the hydrolysis of lupin protein and absorbable at intestinal level, are able to inhibit the protei...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947907/ https://www.ncbi.nlm.nih.gov/pubmed/27424515 http://dx.doi.org/10.1038/srep29931 |
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author | Lammi, Carmen Zanoni, Chiara Aiello, Gilda Arnoldi, Anna Grazioso, Giovanni |
author_facet | Lammi, Carmen Zanoni, Chiara Aiello, Gilda Arnoldi, Anna Grazioso, Giovanni |
author_sort | Lammi, Carmen |
collection | PubMed |
description | Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new useful target for hypercholesterolemia treatment. This work demonstrates that natural peptides, deriving from the hydrolysis of lupin protein and absorbable at intestinal level, are able to inhibit the protein-protein interaction between PCSK9 and the low density lipoprotein receptor (LDLR). In order to sort out the best potential inhibitors among these peptides, a refined in silico model of the PCSK9/LDLR interaction was developed. Docking, molecular dynamics (MD) simulations and peptide binding energy estimations, by MM-GBSA approach, permitted to select the two best candidates among tested peptides that were synthesized and evaluated for their inhibitory activity. The most active was P5 that induced a concentration dependent inhibition of the PCSK9-LDLR binding, with an IC(50) value equal to 1.6 ± 0.33 μM. Tested at a 10 μM concentration, this peptide increased by 66 ± 21.4% the ability of HepG2 cells to take up LDL from the extracellular environment. |
format | Online Article Text |
id | pubmed-4947907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49479072016-07-26 Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells Lammi, Carmen Zanoni, Chiara Aiello, Gilda Arnoldi, Anna Grazioso, Giovanni Sci Rep Article Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new useful target for hypercholesterolemia treatment. This work demonstrates that natural peptides, deriving from the hydrolysis of lupin protein and absorbable at intestinal level, are able to inhibit the protein-protein interaction between PCSK9 and the low density lipoprotein receptor (LDLR). In order to sort out the best potential inhibitors among these peptides, a refined in silico model of the PCSK9/LDLR interaction was developed. Docking, molecular dynamics (MD) simulations and peptide binding energy estimations, by MM-GBSA approach, permitted to select the two best candidates among tested peptides that were synthesized and evaluated for their inhibitory activity. The most active was P5 that induced a concentration dependent inhibition of the PCSK9-LDLR binding, with an IC(50) value equal to 1.6 ± 0.33 μM. Tested at a 10 μM concentration, this peptide increased by 66 ± 21.4% the ability of HepG2 cells to take up LDL from the extracellular environment. Nature Publishing Group 2016-07-18 /pmc/articles/PMC4947907/ /pubmed/27424515 http://dx.doi.org/10.1038/srep29931 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Lammi, Carmen Zanoni, Chiara Aiello, Gilda Arnoldi, Anna Grazioso, Giovanni Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title | Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title_full | Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title_fullStr | Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title_full_unstemmed | Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title_short | Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells |
title_sort | lupin peptides modulate the protein-protein interaction of pcsk9 with the low density lipoprotein receptor in hepg2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947907/ https://www.ncbi.nlm.nih.gov/pubmed/27424515 http://dx.doi.org/10.1038/srep29931 |
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