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 identifi ed putative sorting receptor, sortilin, mas analyzed by surface plasmo n resonance analysis of recombinant RAP and sortilin domains and compa red with binding to megalin and low density lipoprotein receptor-relat ed protein (LRP), The data show that the RAP-binding site in sortilin is localized in the cysteine-rich lumenal part homologous to yeast vac uolar protein-sorting 10 protein (Vps10p), and the sortilin-binding si te 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 o rder: domain III > domain I > domain II. (C) 1998 Federation of Europe an Biochemical Societies.