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Journal article
Molecular Determinants of Plasma Cholesteryl Ester Transfer Protein Binding to High Density Lipoproteins
The Journal of biological chemistry, v 270(19), pp 11532-11542
12 May 1995
PMID: 7744792
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins and is associated with high density lipoproteins (HDL). To understand the mechanism of interaction of CETP with HDL, we studied the binding of pure recombinant CETP to l-palmitoyl-2-oleoylphosphatidylcho-line (POPC)/apoA-I discoidal particles. Separating bound from free CETP using native gradient gel electrophoresis, complexes of CETP with 10-nm hydrodynamic diameter discoidal particles migrated with a diameter of 12–16 nm, compared with ∼7.5 nm for CETP. At lower ratios of CETP to discs, CETP bound to discs without displacement of apoA-I. CETP alone was unable to generate discoidal complexes. Cross-linking and fluorescence resonance energy transfer experiments indicated that CETP bound to discs as monomers. Cross-linking of CETP to apoA-I in discs suggested proximity of apoA-I and CETP. By negative-stain electron microscopy, discoidal complexes containing CETP and CETP monoclonal antibody showed localization of antibody molecules to the disc edge, suggesting that CETP was bound to the disc edge. The binding of CETP to discs of different composition or size was studied. Discs (10-nm Stokes diameter) prepared with either apoA-I or apoA-II had a similar Kd (120 nm). Inclusion of 1 mol % cholesteryl oléate, 5 mol % cholesterol, or 6 mol % phosphatidylinositol increased the binding affinity of CETP 3–10 times (20–30 run). In comparison, plasma HDL3 had a Kd of ∼450 nM. For POPC/apoA-I discs, 10-nm discs bound CETP with much higher affinity than smaller 7.8-nm discs (Kd = 1–2 µm). 7.7-nm hydrodynamic diameter POPC/apoA-I spherical particles containing either triolein or cholesteryl oleate in their core bound CETP with higher affinity (Kd = 50–100 nm) than 7.8-nm POPC/apoA-I discs. Thus, CETP appears to bind to the perimeter of discoidal particles, possibly in a process in which flexible segments in apoA-I or apoA-II accommodate CETP at the disc edge. The binding of CETP to HDL is markedly influenced by overall particle size and shape and by lipid composition, and the increased binding affinity for cholesterol- and cholesteryl ester-containing discs suggests a higher affinity of CETP for nascent than mature HDL.
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Details
- Title
- Molecular Determinants of Plasma Cholesteryl Ester Transfer Protein Binding to High Density Lipoproteins
- Creators
- Can Bruce - Columbia UniversityW. Sean Davidson - Columbia UniversityPaul Kussie - Columbia UniversitySissel Lund-Katz - Columbia UniversityMichael C. Phillips - Columbia UniversityRichik Ghosh - Columbia UniversityAlan R. Tall - Columbia UniversityRajashi Ghosh - School of Education (1997-)
- Publication Details
- The Journal of biological chemistry, v 270(19), pp 11532-11542
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Education
- Web of Science ID
- WOS:A1995QX86500072
- Scopus ID
- 2-s2.0-0029079327
- Other Identifier
- 991019184058004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology