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

J Struct Biol. 2016 May;194(2):191-8. doi: 10.1016/j.jsb.2016.02.016. Epub 2016 Feb 12.


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: Cholesterol transport; Cholesteryl ester transfer protein; Electron microscopy; HDL; HDL remodeling; LDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Antibodies, Monoclonal
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol Esters
  • Epitopes
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Recombinant Proteins