Binding of LRP ligands to the different clusters of ligand-binding repeats. Cysteine-rich ligand-binding repeats (red ovals) in LRP are arranged in four clusters containing 2, 8, 10, and 11 repeats, respectively. Each cluster is followed by 1–4 EGF homology domains (blue), which consist of cysteine-rich EGF repeats (blue circles) and YWTD domains (wavy line). NPxY motifs in the cytoplasmic tail are indicated by the asterisks. No ligand interactions have been mapped to cluster I. Clusters II and IV bind most of the currently mapped known ligands of LRP. Binding of α₂M to clusters II and IV has been found by surface plasmon resonance, although cells transfected with minireceptors containing these clusters do not bind and internalize α₂M (8). ApoE was found to bind to clusters II, III, and IV by ligand blotting. LPL, lipoprotein lipase.