出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein E (apoE) associates with lipoproteins and mediatestheir interaction with members of the LDL receptor family. ApoEexists as three common isoforms that have important distinctfunctional and biological properties. Two apoE isoforms, apoE3and apoE4, are recognized by the LDL receptor, whereas apoE2binds poorly to this receptor and is associated with type IIIhyperlipidemia. In addition, the apoE4 isoform is associatedwith the common late-onset familial and sporadic forms of Alzheimer'sdisease. Although the interaction of apoE with the LDL receptoris well characterized, the specificity of other members of thisreceptor family for apoE is poorly understood. In the currentinvestigation, we have characterized the binding of apoE tothe VLDL receptor and the LDL receptor-related protein (LRP).
Our results indicate that like the LDL receptor, LRP preferslipid-bound forms of apoE, but in contrast to the LDL receptor,both LRP and the VLDL receptor recognize all apoE isoforms.Interestingly, the VLDL receptor does not require the associationof apoE with lipid for optimal recognition and avidly bindslipid-free apoE. It is likely that this receptor-dependent specificityfor various apoE isoforms and for lipid-free versus lipid-boundforms of apoE is physiologically significant and is connectedto distinct functions for these receptors.Abbreviations: AD, Alzheimer's disease; apoE, apolipoprotein E; LRP, low density lipoprotein receptor-related protein; RAP, receptor-associated protein; Rmax, maximal change in response units; RU, resonance units; SPR, surface plasmon resonance; sVLDLr1–8, soluble very low density lipoprotein receptor fragment containing ligand binding repeats 1–8
Supplementary key words apolipoprotein E • low density lipoprotein • very low density lipoprotein • low density lipoprotein receptor-related protein
