Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP.
Détails
ID Serval
serval:BIB_EDA732AF88DE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP.
Périodique
Journal of structural biology
ISSN
1095-8657 (Electronic)
ISSN-L
1047-8477
Statut éditorial
Publié
Date de publication
05/2016
Peer-reviewed
Oui
Volume
194
Numéro
2
Pages
191-198
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
The cholesteryl ester transfer protein (CETP) enables the transfer of cholesteryl ester (CE) from high-density lipoproteins (HDL) to low-density lipoproteins (LDL) in the plasma compartment. CETP inhibition raises plasma levels of HDL cholesterol; a ternary tunnel complex with CETP bridging HDL and LDL was suggested as a mechanism. Here, we test whether the inhibition of CETP tunnel complex formation is a promising approach to suppress CE transfer from HDL to LDL, for potential treatment of cardio-vascular disease (CVD). Three monoclonal antibodies against different epitopes of CETP are assayed for their potential to interfere with CE transfer between HDL and/or LDL. Surprisingly, antibodies that target the tips of the elongated CETP molecule, interaction sites sterically required to form the suggested transfer complexes, do not interfere with CETP activity, but an antibody binding to the central region does. We show that CETP interacts with HDL, but not with LDL. Our findings demonstrate that a ternary tunnel complex is not the mechanistic prerequisite to transfer CE among lipoproteins.
Mots-clé
Antibodies, Monoclonal/chemistry, Antibodies, Monoclonal/isolation & purification, Biological Transport, Cell Line, Cholesterol Ester Transfer Proteins/genetics, Cholesterol Ester Transfer Proteins/metabolism, Cholesterol Ester Transfer Proteins/ultrastructure, Cholesterol Esters/metabolism, Epitopes/chemistry, Epitopes/ultrastructure, Gene Expression, Humans, Lipoproteins, HDL/metabolism, Lipoproteins, HDL/ultrastructure, Lipoproteins, LDL/metabolism, Lipoproteins, LDL/ultrastructure, Microscopy, Electron, Transmission, Protein Binding, Recombinant Proteins/genetics, Recombinant Proteins/metabolism, Recombinant Proteins/ultrastructure, Cholesterol transport, Cholesteryl ester transfer protein, Electron microscopy, HDL, HDL remodeling, LDL
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/06/2023 16:02
Dernière modification de la notice
20/07/2023 6:57