Two Apolipoprotein E Mimetic Peptides, ApoE(130−149) and ApoE(141−155)2, Bind to LRP1

Abstract

LRP1 is a cell surface receptor responsible for clearing some 30 known ligands. We have previously shown that each of the three complete LDL receptor-homology domains of the LRP1 extracellular domain (sLRPs) binds apoE-enriched β-VLDL particles. Here we show that two peptides from the N-terminal receptor binding domain of apoE, which are known to elicit a number of different cellular responses, bind to LRP1. Solution binding assays show that the two peptides, apoE(130−149) and apoE(141−155)², interact with each of the sLRPs (2, 3, and 4). Each peptide was found to exhibit the same solution binding characteristics as apoE-enriched β-VLDL particles. Surface plasmon resonance analyses of the sLRP−apoE peptide interaction show that both peptides bind the sLRPs with K_D values in the 100 nM range, a value similar to the effective concentration required for observation of the cellular responses. Consistent with results from mutagenesis studies of binding of apoE to LDLR, apoE(130−149,Arg142Glu) bound with a K_D similar to that of the wild-type sequence, while apoE(130−149,Lys143Glu) showed a 10-fold decrease in K_D. Each of the peptides bound heparin, and heparin competed for sLRP binding.