Binding of amphiphilic peptides to phospholipid/cholesterol unilamellar vesicles: a model for protein--cholesterol interaction. 1981

D Fukushima, and S Yokoyama, and F J Kézdy, and E T Kaiser

In earlier studies, we prepared a docosapeptide, 1, designed with minimum homology as an amphiphilic alpha-helical model of apolipoprotein A-I (apo A-I) and described its lipid-binding characteristics, surface properties, and enzyme-activating ability. Although the affinity of 1 for egg lecithin unilamellar vesicles was comparable with that for the binding of apo A-I, the affinity of 1 for mixed lecithin/cholesterol (4:1 mol/mol) vesicles was less than that of apo A-I. It appeared possible that the 3-hydroxyl group of cholesterol may have a deleterious interaction with the hydrophobic portion of the amphiphilic helix of 1 that is inserted into the vesicles. Examination of the amphiphilic alpha-helical segments of apo A-I suggested that the preferential interaction of apo A-I with the mixed vesicles might be due to the presence of polar arginine residues in the otherwise hydrophobic regions of two of the helices. Therefore, we synthesized a model docosapeptide, 2, corresponding to the sequence of 1 but containing arginine rather than leucine at position 10 in the hydrophobic region of the alpha helix to assess the role of the alcohol function of cholesterol in protein--cholesterol interactions. The results of studies on the binding of 2 to unilamellar vesicles containing lecithin only, lecithin/cholesterol, lecithin/cholesterol hemisuccinate, or lecithin/cholesterol methyl ether were consistent with the postulate that the major role of cholesterol in the binding of proteins to phospholipid surfaces is the creation of free space between the phospholipid head groups that can accommodate the amphiphilic peptide chains at the interface.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008075 Lipoproteins, HDL A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases. High Density Lipoprotein,High-Density Lipoprotein,High-Density Lipoproteins,alpha-Lipoprotein,alpha-Lipoproteins,Heavy Lipoproteins,alpha-1 Lipoprotein,Density Lipoprotein, High,HDL Lipoproteins,High Density Lipoproteins,Lipoprotein, High Density,Lipoprotein, High-Density,Lipoproteins, Heavy,Lipoproteins, High-Density,alpha Lipoprotein,alpha Lipoproteins
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001053 Apolipoproteins Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES. Apolipoprotein

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