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PMID:17326667

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Citation

Nilsson, SK, Lookene, A, Beckstead, JA, Gliemann, J, Ryan, RO and Olivecrona, G (2007) Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family. Biochemistry 46:3896-904

Abstract

Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by the receptor associated protein, a known ligand for members of the low density lipoprotein receptor family. Preincubation with heparin decreased the receptor binding of apolipoprotein A-V, indicating that overlap exists between the recognition sites for these receptors and for heparin. A double mutant, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins.

Links

PubMed Online version:10.1021/bi7000533

Keywords

Amino Acid Substitution; Apolipoproteins A/chemistry; Apolipoproteins A/genetics; Apolipoproteins A/metabolism; Calcium/chemistry; Calcium/metabolism; Endocytosis/physiology; Heparin/chemistry; Heparin/metabolism; Homeostasis/genetics; Humans; LDL-Receptor Related Proteins/chemistry; LDL-Receptor Related Proteins/metabolism; Lipid Metabolism/physiology; Membrane Transport Proteins/chemistry; Membrane Transport Proteins/metabolism; Plasma/chemistry; Plasma/metabolism; Protein Binding/genetics; Surface Plasmon Resonance

Significance

Annotations

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

HUMAN:AMRP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q07954

F

Seeded From UniProt

complete

HUMAN:AMRP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92673

F

Seeded From UniProt

complete

HUMAN:LRP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P30533

F

Seeded From UniProt

complete

HUMAN:LRP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q6Q788

F

Seeded From UniProt

complete

HUMAN:SORL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P30533

F

Seeded From UniProt

complete

HUMAN:APOE

enables

GO:0050750: low-density lipoprotein particle receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92673

F

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0050750: low-density lipoprotein particle receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q07954

F

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0050750: low-density lipoprotein particle receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92673

F

Seeded From UniProt

complete

HUMAN:APOA5

enables

GO:0008201: heparin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SORL

enables

GO:0030169: low-density lipoprotein particle binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q6Q788

F

Seeded From UniProt

complete

HUMAN:SORL

enables

GO:0030169: low-density lipoprotein particle binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P02649

F

Seeded From UniProt

complete


See also

References

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