Quantitative dissection of the binding contributions of ligand lysines of the receptor-associated protein (RAP) to the low density lipoprotein receptor-related protein (LRP1)

Abstract

Background: Only small effects on affinity are seen for seemingly critical lysines of LRP1 ligand RAP. Results: Lysines act in pairs and fully account for overall affinity to LRP1. Mutagenesis reduces binding up to 100,000-fold. Conclusion: Two pairs of paired lysine interactions can give high affinity binding of protein ligands to LRP1. Significance: Rules for identifying high affinity receptor binding sites are established. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.