The megalin chimeric receptor containing the SNX17 binding domain of LRP1 interacts with SNX17. (A) Schematic diagrams of the cytoplasmic domains of LRP1 (full-length tail of 100 amino acids and T14-45, constructs “a” and “b”, respectively) and megalin (wild-type, full-length tail, 209-amino acid construct “c” and chimeras “d–e”). Residue number 4 is the fourth amino acid following the transmembrane domain of the LRP1 tail. Constructs “d” and “e” correspond to megalin tails containing the wild-type or mutant SNX17-binding domain, respectively, after the thirteenth amino acid following the transmembrane domain. The tail proteins were fused to GST. The mutant SNX17-binding domain contains a Y to A mutation. (B) GST pull-down assays using the megalin tail constructs containing the wild-type and mutant SNX17-binding domain. GST serves as a negative control and GST-LRP1 tail (full-length) and T14-45 were the positive controls. The presence of the SNX17-binding domain within the megalin tail (as shown in construct “d”) supports its binding to SNX17.