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PMID:12810715

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Citation

Weinberg, RB, Cook, VR, Beckstead, JA, Martin, DD, Gallagher, JW, Shelness, GS and Ryan, RO (2003) Structure and interfacial properties of human apolipoprotein A-V. J. Biol. Chem. 278:34438-44

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.

Links

PubMed Online version:10.1074/jbc.M303784200

Keywords

Air; Animals; Apolipoproteins/metabolism; Apolipoproteins A/chemistry; Apolipoproteins A/genetics; COS Cells; Endoplasmic Reticulum/metabolism; Golgi Apparatus/metabolism; Humans; Hydrogen-Ion Concentration; Kinetics; Lipid Metabolism; Lipids/chemistry; Lipoproteins, VLDL/metabolism; Microscopy, Fluorescence; Polymorphism, Genetic; Protein Binding; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Software; Spectrometry, Fluorescence; Spectrophotometry; Time Factors; Water/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:APOA1

enables

GO:0005543: phospholipid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0005543: phospholipid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0008289: lipid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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