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Title: Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids

Abstract

Highlights: •The secondary structure of a C-terminal peptide derived from CETP was studied. •Lipids modulate secondary structure changes of a C-terminal peptide derived from CETP. •Lysophosphatidic acid maintains a functional α-helix and prevents fibril formation. •Transfer of lipids by CETP is related to the presence of an α-helix at its C-end. -- Abstract: Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus residues we have previously shown that mutation D{sub 470}N promotes a conformational change towards a β-secondary structure. In turn, this modification leads to the formation of oligomers and fibrillar structures, which cause cytotoxic effects similar to the ones provoked by amyloid peptides. In this study, we evaluated the role of specific lipid arrangements on the structure of peptide helix-Z (D{sub 470}N) through the use of thioflavin T fluorescence, peptide bond absorbance, circular dichroism and electron microscopy. The results indicate that the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid (LPA) under neutral pH induce a conformational transition of peptide helix-Z containing a β-sheet conformation to a native α-helix structure, therefore avoiding the formation of amyloid fibrils. In contrast, incubation with phosphatidic acid does not changemore » the profile for the β-sheet conformation. When the electrostatic charge at the surface of micelles or vesicles is regulated through the use of lipids such as phospholipid and LPA, minimal changes and the presence of β-structures were recorded. Mixtures with a positive net charge diminished the percentage of β-structure and the amount of amyloid fibrils. Our results suggest that the degree of solvation determined by the presence of a free hydroxyl group on lipids such as LPA is a key condition that can modulate the secondary structure and the consequent formation of amyloid fibrils in the highly flexible C-terminus domain of CETP.« less

Authors:
 [1];  [1]
  1. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, DF (Mexico)
Publication Date:
OSTI Identifier:
22239558
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 434; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBON 12; CONFORMATIONAL CHANGES; ELECTRON MICROSCOPY; FLUORESCENCE; HYDROXIDES; LIPOPROTEINS; PEPTIDES; PHOSPHOLIPIDS

Citation Formats

García-González, Victor, Mas-Oliva, Jaime, and División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF. Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.03.067.
García-González, Victor, Mas-Oliva, Jaime, & División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF. Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids. United States. https://doi.org/10.1016/J.BBRC.2013.03.067
García-González, Victor, Mas-Oliva, Jaime, and División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF. 2013. "Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids". United States. https://doi.org/10.1016/J.BBRC.2013.03.067.
@article{osti_22239558,
title = {Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids},
author = {García-González, Victor and Mas-Oliva, Jaime and División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF},
abstractNote = {Highlights: •The secondary structure of a C-terminal peptide derived from CETP was studied. •Lipids modulate secondary structure changes of a C-terminal peptide derived from CETP. •Lysophosphatidic acid maintains a functional α-helix and prevents fibril formation. •Transfer of lipids by CETP is related to the presence of an α-helix at its C-end. -- Abstract: Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus residues we have previously shown that mutation D{sub 470}N promotes a conformational change towards a β-secondary structure. In turn, this modification leads to the formation of oligomers and fibrillar structures, which cause cytotoxic effects similar to the ones provoked by amyloid peptides. In this study, we evaluated the role of specific lipid arrangements on the structure of peptide helix-Z (D{sub 470}N) through the use of thioflavin T fluorescence, peptide bond absorbance, circular dichroism and electron microscopy. The results indicate that the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid (LPA) under neutral pH induce a conformational transition of peptide helix-Z containing a β-sheet conformation to a native α-helix structure, therefore avoiding the formation of amyloid fibrils. In contrast, incubation with phosphatidic acid does not change the profile for the β-sheet conformation. When the electrostatic charge at the surface of micelles or vesicles is regulated through the use of lipids such as phospholipid and LPA, minimal changes and the presence of β-structures were recorded. Mixtures with a positive net charge diminished the percentage of β-structure and the amount of amyloid fibrils. Our results suggest that the degree of solvation determined by the presence of a free hydroxyl group on lipids such as LPA is a key condition that can modulate the secondary structure and the consequent formation of amyloid fibrils in the highly flexible C-terminus domain of CETP.},
doi = {10.1016/J.BBRC.2013.03.067},
url = {https://www.osti.gov/biblio/22239558}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 434,
place = {United States},
year = {Fri Apr 26 00:00:00 EDT 2013},
month = {Fri Apr 26 00:00:00 EDT 2013}
}