The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin

Binding of the receptor-associated protein (RAP) to the newly identified putative sorting receptor, sortilin, mas analyzed by surface plasmon resonance analysis of recombinant RAP and sortilin domains and compared with binding to megalin and low density lipoprotein receptor-related protein (LRP), The data show that the RAP-binding site in sortilin is localized in the cysteine-rich lumenal part homologous to yeast vacuolar protein-sorting 10 protein (Vps10p), and the sortilin-binding site in RAP is localized in the carboxy-terminal domain III of the three homologous domains in RAP, Whereas sortilin bound only RAP domain III, megalin and LRP bound all RAP domains with the functional affinity order: domain III > domain I > domain II. (C) 1998 Federation of European Biochemical Societies.