Recognition of Unique Carboxyl-Terminal Motifs by Distinct PDZ Domains

TLDR

The authors used an oriented peptide library to probe the binding specificities of nine PDZ domains, and crystal structures of the PSD‑95‑3 PDZ domain clarified the observed preferences. The study found that each PDZ domain prefers hydrophobic residues at the C‑terminus, with distinct optimal motifs: the DLG family favors Glu‑(Ser/Thr)‑X‑(Val/Ile), whereas the LIN‑2, p55, and Tiam‑1 families favor hydrophobic or aromatic residues in the last three positions.

Abstract

The oriented peptide library technique was used to investigate the peptide-binding specificities of nine PDZ domains. Each PDZ domain selected peptides with hydrophobic residues at the carboxyl terminus. Individual PDZ domains selected unique optimal motifs defined primarily by the carboxyl terminal three to seven residues of the peptides. One family of PDZ domains, including those of the Discs Large protein, selected peptides with the consensus motif Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any amino acid) at the carboxyl terminus. In contrast, another family of PDZ domains, including those of LIN-2, p55, and Tiam-1, selected peptides with hydrophobic or aromatic side chains at the carboxyl terminal three residues. On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the peptide library can be rationalized.