Selection of a Peptide Ligand to the p75 Neurotrophin Receptor Death Domain and Determination of Its Binding Sites by NMR

Abstract

The p75 neurotrophin receptor (p75NTR) contains a conserved death domain module similar to that of the cytotoxic receptors Fas and TNFR-1. Here, we describe the selection of peptide ligands from a combinatorial library using a variation of the selectively-infective phage (SIP) method directed to the death domain of p75NTR. The binding sites on the death domain of p75NTRwere identified for a 15 amino acid residue peptide by nuclear magnetic resonance (NMR) spectroscopy. The selected peptides may be useful for probing the function of the p75NTRdeath domain and aid in defining its downstream signalling mechanism.