Two apolipoprotein E mimetic peptides, ApoE(130-149) and ApoE(141-155)2, bind to LRP1.
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 beta-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 beta-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.
Croy
Johnny E
JE
Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0378, USA.
Brandon
Theodore
T
Komives
Elizabeth A
EA
D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D002942:Circular Dichroism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000378:metabolism*; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D012996:Solutions; D020349:Surface Plasmon Resonance
D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D008081:Liposomes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; D012996:Solutions; D006493:Heparin