The molecular mechanism of lipoprotein binding by the low-density lipoprotein (LDL) receptor (LDLR) is poorly understood, one reason being that structures of lipoprotein–receptor complexes are not available. LDLR uses calcium-binding repeats (LRs) to interact with apolipoprotein B and apolipoprotein E (ApoB and ApoE). We have used NMR and SPR to characterize the complexes formed by LR5 and three peptides encompassing the putative binding regions of ApoB (site A and site B) and ApoE. The three peptides bind at the hydrophilic convex face of LR5, forming complexes that are weakened at low [Ca2+] and low pH. Thus, endosomal conditions favour dissociation of LDLR/lipoprotein complexes regardless of whether active displacement of bound lipoproteins by the β-propeller in LDLR takes place. The multiple ApoE copies in β very low density lipoproteins (β-VLDLs), and the presence of two competent binding sites (A and B) in LDLs, suggest that LDLR chelates lipoproteins and enhances complex affinity by using more than one LR.