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HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.
- Source :
-
Scientific reports [Sci Rep] 2015 Mar 04; Vol. 5, pp. 8741. Date of Electronic Publication: 2015 Mar 04. - Publication Year :
- 2015
-
Abstract
- Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.
- Subjects :
- Cholesterol Ester Transfer Proteins genetics
Cholesterol Ester Transfer Proteins ultrastructure
Cryoelectron Microscopy
Electron Microscope Tomography
Humans
Hydrophobic and Hydrophilic Interactions
Imaging, Three-Dimensional
Lipoproteins, HDL blood
Lipoproteins, HDL ultrastructure
Liposomes chemistry
Liposomes metabolism
Liposomes ultrastructure
Membrane Lipids chemistry
Microscopy, Electron, Transmission
Protein Binding
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Recombinant Proteins ultrastructure
Cholesterol Ester Transfer Proteins metabolism
Lipoproteins, HDL metabolism
Membrane Lipids metabolism
Molecular Dynamics Simulation
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 25737239
- Full Text :
- https://doi.org/10.1038/srep08741