Characterization of apolipoprotein A-V structure and mode of plasma triacylglycerol regulation.
OBJECTIVE
Cardiovascular disease is the leading cause of death in the USA, and hypertriglyceridemia represents an independent risk factor contributing to its premature onset. Apolipoprotein (apo)A-V has been shown to be a potent regulator of plasma triacylglycerol. We highlight structural aspects of apoA-V and discuss recent findings that provide mechanistic insight into its function as a regulator of plasma triacylglycerol metabolism.


RESULTS
Recent findings indicate that apoA-V is comprised of two independently folded domains. Fluorescence spectroscopy and truncation analysis revealed that the carboxyl-terminal region functions in apoA-V lipid binding, consistent with its known association with plasma lipoproteins. An indirect triacylglycerol-modulating effect of apoA-V has been attributed to heparan sulfate proteoglycan binding, as confirmed by structural studies. Furthermore, apoA-V has been shown to interact with cell surface receptors, potentially facilitating lipoprotein particle endocytosis.


CONCLUSIONS
Several features of apoA-V, including extremely low plasma concentration, lack of correlation with plasma cholesterol levels despite its association with HDL, and insolubility at neutral pH in the absence of lipid, are unlike those of other exchangeable apolipoproteins. Current and future studies of apoA-V will help to shed light on the molecular basis whereby this protein functions to modulate plasma lipid homeostasis.
Wong
Kasuen
K
Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Ryan
Robert O
RO
D000818:Animals; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000737:chemistry* / Q000502:physiology*; D004705:Endocytosis; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D014280:Triglycerides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D019812:Heparan Sulfate Proteoglycans; D008055:Lipids; D014280:Triglycerides