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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Lauer Matthias E, Graff-Meyer Alexandra, Rufer Arne C, Maugeais Cyrille, von der Mark Elisabeth, Matile Hugues, D'Arcy Brigitte, Magg Christine, Ringler Philippe, Müller Shirley A, Scherer Sebastian, Dernick Gregor, Thoma Ralf, Hennig Michael, Niesor Eric J, Stahlberg Henning,
Project Electron Microscopy of Membrane Proteins
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Original article (peer-reviewed)

Journal Journal of structural biology
Volume (Issue) 194(2)
Page(s) 191 - 8
Title of proceedings Journal of structural biology
DOI 10.1016/j.jsb.2016.02.016

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.
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