title: Key structural arrangements at the C-terminus domain of CETP suggest a potential mechanism for lipid-transfer activity.
abstract: The cholesteryl-ester transfer protein (CETP) promotes cholesteryl-ester and triglyceride transfer between lipoproteins. We evaluated the secondary structure stability of a series of small peptides derived from the C-terminus of CETP in a wide range of pH's and lipid mixtures, and studied their capability to carry out disorder-to-order secondary structure transitions dependent of lipids. We report that while a mixture of phosphatidylcholine/cholesteryl-esters forms large aggregated particles, the inclusion of a series of CETP carboxy-terminal peptides in a stable α-helix conformation, allows the formation of small homogeneous micelle-like structures. This phenomenon of lipid ordering was directly connected to secondary structural transitions at the C-terminus domain when lysophosphatidic acid and lysophosphatidylcholine lipids were employed. Circular dichroism, cosedimentation experiments, electron microscopy, as well as molecular dynamics simulations confirm this phenomenon. When purified CETP is studied, the same type of phenomenon occurs by promoting the reorganization of lipid from large to smaller particles. Our findings extend the emerging view for a novel mechanism of lipid transfer carried out by CETP, assigning its C-terminus domain the property to accomplish lipid ordering through secondary structure disorder-to-order transitions.
authors: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D.F., Mexico.
authors: Victor
authors: V
authors: García-González
authors: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D.F., Mexico.
authors: Nadia
authors: N
authors: Gutiérrez-Quintanar
authors: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D.F., Mexico.
authors: Paola
authors: P
authors: Mendoza-Espinosa
authors: Departamento de Física Aplicada, Facultad de Física, Universidad de Santiago de Compostela, Spain.
authors: Pilar
authors: P
authors: Brocos
authors: Departamento de Física Aplicada, Facultad de Física, Universidad de Santiago de Compostela, Spain.
authors: Angel
authors: A
authors: Piñeiro
authors: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D.F., Mexico; División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico. Electronic address: jmas@ifc.unam.mx.
authors: Jaime
authors: J
authors: Mas-Oliva
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D053480:Cholesterol Ester Transfer Proteins / Q000737:chemistry*; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008246:Lysophospholipids; D008823:Micelles; D010446:Peptide Fragments; C032881:lysophosphatidic acid
keywords: C-terminus domain; CETP; Lipid micelles; Lipid ordering; Secondary structure transitions