Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP.

Details

Serval ID
serval:BIB_EDA732AF88DE
Type
Article: article from journal or magazin.
Collection
Publications
Title
Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP.
Journal
Journal of structural biology
Author(s)
Lauer M.E., Graff-Meyer A., Rufer A.C., Maugeais C., von der Mark E., Matile H., D'Arcy B., Magg C., Ringler P., Müller S.A., Scherer S., Dernick G., Thoma R., Hennig M., Niesor E.J., Stahlberg H.
ISSN
1095-8657 (Electronic)
ISSN-L
1047-8477
Publication state
Published
Issued date
05/2016
Peer-reviewed
Oui
Volume
194
Number
2
Pages
191-198
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
09/06/2023 16:02
Last modification date
20/07/2023 6:57
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