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The LDL receptor (LDLR) internalizes LDL and VLDL particles In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the Ligand Binding domain (LR4-5) and a β-propeller motif. Here, we investigate by SPR the interactions between those two modules and the β-propeller. Our results indicate that the two modules cooperate to bind the β-propeller. The binding is favored by low pH and by high [Ca++]. Our data show that Mg++, at high concentration in the endosome, favors the formation of the closed conformation by replacing the structuring effect of Ca++ in LR5. We propose a sequential model of LDL release where formation of the close conformation follo... More