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

Lauer, Matthias E. and Graff-Meyer, Alexandra and Rufer, Arne C. and Maugeais, Cyrille and von der Mark, Elisabeth and Matile, Hugues and D'Arcy, Brigitte and Magg, Christine and Ringler, Philippe and Müller, Shirley A. and Scherer, Sebastian and Dernick, Gregor and Thoma, Ralf and Hennig, Michael and Niesor, Eric J. and Stahlberg, Henning. (2016) Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP. Journal of Structural Biology, 194 (2). pp. 191-198.

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Official URL: http://edoc.unibas.ch/42159/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:1047-8477
e-ISSN:1095-8657
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 Apr 2018 14:13
Deposited On:29 Sep 2016 07:37

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