title: Structure and interfacial properties of human apolipoprotein A-V.
abstract: Apolipoprotein A-V (apoA-V), the newest member of the plasma apolipoprotein family, was recently discovered by comparison of the mouse and human genomes. Studies in rodents and population surveys of human apoA-V polymorphisms have noted a strong effect of apoA-V on plasma triglyceride levels. Toward the elucidation of the biologic function of apoA-V, we used spectroscopic and surface chemistry techniques to probe its structure and interfacial activity. Computer-assisted sequence analysis of apoA-V predicts that it is very hydrophobic, contains a significant amount of alpha-helical secondary structure, and probably is composed of discrete structural regions with varying degrees of lipid affinity. Fluorescence spectroscopy of recombinant human apoA-V provided evidence of tertiary folding, and light scattering studies indicated that apoA-V transforms dimyristoylphosphatidylcholine vesicles into discoidal complexes with an efficiency similar to that of apoA-I. Surface chemistry techniques revealed that apoA-V displays high affinity, low elasticity, and slow binding kinetics at hydrophobic interfaces, properties we propose may retard triglyceride-rich particle assembly. Metabolic labeling and immunofluorescence studies of COS-1 cells transfected with human apoA-V demonstrated that apoA-V is poorly secreted, remains associated with the endoplasmic reticulum, and does not traffic to the Golgi. Given that overexpression of the apoA-V gene lowers plasma triglycerides in mice, these data together suggest that apoA-V may function intracellularly to modulate hepatic VLDL synthesis and/or secretion.
authors.affiliation: Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. weinberg@wfubmc.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Weinberg
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Cook
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Beckstead
authors.forename: Dale D O
authors.initials: DD
authors.lastname: Martin
authors.forename: James W
authors.initials: JW
authors.lastname: Gallagher
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Shelness
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
mesh_terms: D000388:Air; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000378:metabolism; D001054:Apolipoproteins A / Q000737:chemistry* / Q000235:genetics*; D019556:COS Cells; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012984:Software; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D008055:Lipids; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D014867:Water