Next Article in Journal
Recent Advances in Conjugated Polymers for Light Emitting Devices
Next Article in Special Issue
Self-Assembly, Surface Activity and Structure of n-Octyl-β-D-thioglucopyranoside in Ethylene Glycol-Water Mixtures
Previous Article in Journal
Continuous Spatial Tuning of Laser Emissions in a Full Visible Spectral Range
Previous Article in Special Issue
Coupled Folding and Specific Binding: Fishing for Amphiphilicity
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2011, 12(3), 2019-2035; doi:10.3390/ijms12032019

Amyloidogenic Properties of a D/N Mutated 12 Amino Acid Fragment of the C-Terminal Domain of the Cholesteryl-Ester Transfer Protein (CETP)

Institute of Cell Physiology, National Autonomus University of Mexico (UNAM), AP 70-243, 04510 Mexico, D.F., Mexico
*
Author to whom correspondence should be addressed.
Received: 10 January 2011 / Revised: 2 March 2011 / Accepted: 14 March 2011 / Published: 21 March 2011
(This article belongs to the Special Issue Advances in Molecular Recognition)
View Full-Text   |   Download PDF [1328 KB, uploaded 19 June 2014]   |  

Abstract

The cholesteryl-ester transfer protein (CETP) facilitates the transfer of cholesterol esters and triglycerides between lipoproteins in plasma where the critical site for its function is situated in the C-terminal domain. Our group has previously shown that this domain presents conformational changes in a non-lipid environment when the mutation D470N is introduced. Using a series of peptides derived from this C-terminal domain, the present study shows that these changes favor the induction of a secondary β-structure as characterized by spectroscopic analysis and fluorescence techniques. From this type of secondary structure, the formation of peptide aggregates and fibrillar structures with amyloid characteristics induced cytotoxicity in microglial cells in culture. These supramolecular structures promote cell cytotoxicity through the formation of reactive oxygen species (ROS) and change the balance of a series of proteins that control the process of endocytosis, similar to that observed when β-amyloid fibrils are employed. Therefore, a fine balance between the highly dynamic secondary structure of the C-terminal domain of CETP, the net charge, and the physicochemical characteristics of the surrounding microenvironment define the type of secondary structure acquired. Changes in this balance might favor misfolding in this region, which would alter the lipid transfer capacity conducted by CETP, favoring its propensity to substitute its physiological function. View Full-Text
Keywords: cholesteryl-ester transfer protein (CETP); CETP C-terminal domain; α-helix and β-sheet secondary structures; peptide oligomers; amyloids cholesteryl-ester transfer protein (CETP); CETP C-terminal domain; α-helix and β-sheet secondary structures; peptide oligomers; amyloids
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

García-González, V.; Mas-Oliva, J. Amyloidogenic Properties of a D/N Mutated 12 Amino Acid Fragment of the C-Terminal Domain of the Cholesteryl-Ester Transfer Protein (CETP). Int. J. Mol. Sci. 2011, 12, 2019-2035.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top