RECOGNITION OF UNIQUE CARBOXYL-TERMINAL MOTIFS BY DISTINCT PDZ DOMAINS

The oriented peptide library technique was used to investigate the pep tide-binding specificities of nine PDZ domains. Each PDZ domain select ed peptides with hydrophobic residues at the carboxyl terminus. Indivi dual PDZ domains selected unique optimal motifs defined primarily by t he carboxyl terminal three to seven residues of the peptides. One fami ly of PDZ domains, including those of the Discs Large protein, selecte d peptides with the consensus motif Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any ami no acid) at the carboxyl terminus. in contrast , another ami ly of PDZ domains, including those of LIN-2, p55, and Ti am-1, selected peptides with hydrophobic or aromatic side chains at th e carboxyl terminal three residues. On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the pepti de library can be rationalized.