title: Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL(-).
abstract: A subpopulation of low-density lipoproteins (LDL) is present in human plasma that contains lipid hydroperoxides and is more negatively charged (LDL(-)) than normal native LDL. By circular dichroism and tryptophan lifetime measurements we found that apoB-100 secondary structure is markedly decreased and its conformation is severely altered in LDL(-). The low tryptophan fluorescence intensity confirms the oxidative degradation of the lipoprotein, and the very long lifetime value of one of its decay components indicates a low polarity environment for the remaining unbleached residues. Either a peculiar folding or, most likely, a sinking of the apoB-100 into the lipid core can account for the observed long lifetime component. Oxidation in vitro produces a similar unfolding of the apolipoprotein but the lifetime of tryptophan fluorescence is shifted to lower values, indicating that the denatured apoprotein remains at the hydrophilic surface of the lipoprotein particle. A disordering and an increased polarity of the LDL(-) surface lipids was demonstrated by measuring the generalized polarization of 2-dimethylamino-6-lauroylnaphthalene (Laurdan). The looser monolayer packing apparently favors the new conformation of apoB-100 and its sinking into a more hydrophobic environment, possibly accounting for it reduced receptor binding properties.
authors: Istituto di Medicina Sperimentale, CNR, Roma, Italy.
authors: T
authors: T
authors: Parasassi
authors: G
authors: G
authors: Bittolo-Bon
authors: R
authors: R
authors: Brunelli
authors: G
authors: G
authors: Cazzolato
authors: E K
authors: EK
authors: Krasnowska
authors: G
authors: G
authors: Mei
authors: A
authors: A
authors: Sevanian
authors: F
authors: F
authors: Ursini
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007848:Laurates / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry; D014680:Veins / Q000502:physiology
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D005456:Fluorescent Dyes; D007848:Laurates; D008077:Lipoproteins, LDL; D014364:Tryptophan; D006861:Hydrogen Peroxide; D015081:2-Naphthylamine; C065580:laurdan