title: Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus.
abstract: We have previously shown that the synthetic peptide apoE(129-169) forms lipid-peptide complexes with dimyristoylphosphatidylcholine (DMPC) with an L:P molar ratio of 125:1; the peptide in the isolated complex contains approximately 56% alpha-helicity. These results verify the presence of an amphipathic alpha-helix in this region of apoE as predicted by Chou-Fasman analysis and hydrophobicity calculations. To further define the lipid binding regions of apoE, we have synthesized four peptides, apoE(211-243), -(202-243), -(267-286), and -(263-286), from the carboxyl terminus of apoE and studied their lipid binding properties; apoE(202-243) contains two potential amphipathic helices. Although all four peptides formed alpha-helices in the helix-forming solvent 30% hexafluoropropanol, we found that only apoE(263-286) formed a stable complex with DMPC. The peptide contained approximately 80% alpha-helicity, and its Trp fluorescence spectrum was blue-shifted by 20 nm in the complex which had an L:P ratio of 163:1. We conclude that this sequence is a newly identified lipid binding region of apoE and that the amphipathic helices 203-221 and 226-243 are too hydrophilic to bind phospholipid.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: J T
authors.initials: JT
authors.lastname: Sparrow
authors.forename: D A
authors.initials: DA
authors.lastname: Sparrow
authors.forename: G
authors.initials: G
authors.lastname: Fernando
authors.forename: A R
authors.initials: AR
authors.lastname: Culwell
authors.forename: M
authors.initials: M
authors.lastname: Kovar
authors.forename: A M
authors.initials: AM
authors.lastname: Gotto
mesh_terms: D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000737:chemistry*; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D011485:Protein Binding
chemical_list: D001057:Apolipoproteins E; D010455:Peptides; D004134:Dimyristoylphosphatidylcholine