title: Structural and functional properties of natural and chemical variants of apolipoprotein A-I.
abstract: Four isoforms of human apolipoprotein A-I (apo A-I): the normal allele product and the corresponding Lys-107 deletion mutant, and apo A-I with sulfoxidized Met-112 and Met-148 residues and the corresponding reduced form, were investigated in their lipid binding properties, structures, and abilities to activate lecithin-cholesterol acyltransferase. All apo A-I isoforms reacted completely with palmitoyloleoylphosphatidylcholine to give reconstituted high density lipoprotein (rHDL) particles with diameters of 96 A. These particles reacted with low density lipoprotein (LDL) and lecithin-cholesterol acyltransferase (LCAT) equally well, except that the Lys-107 deletion mutant was resistant to structural rearrangements in the presence of LDL. The spectral measurements revealed only minor structural differences among the free apo A-I forms or among their rHDL products, but showed a decreased stability of the Lys-107 deletion mutant and the isoform with reduced Met towards denaturation by guanidine hydrochloride. The results demonstrate that these specific alterations of the apo A-I sequence, which change the helix orientation and hydrophobic moment in one or two putative lipid binding regions, are not sufficient to disrupt the overall properties of the apo A-I complexes with lipid nor to impair significantly their ability to activate LCAT.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Illinois, Urbana 61801.
authors.forename: A
authors.initials: A
authors.lastname: Jonas
authors.forename: A
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: L
authors.initials: L
authors.lastname: Churgay
authors.forename: W W
authors.initials: WW
authors.lastname: Mantulin
authors.forename: G
authors.initials: G
authors.lastname: Assmann
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation; D017353:Gene Deletion; D008239:Lysine; D008969:Molecular Sequence Data; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D016632:Apolipoprotein A-I; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008239:Lysine