Z. Songyang,
*
A. S. Fanning,
C. Fu,
J. Xu,
S. M. Marfatia,
A. H. Chishti,
A. Crompton,
A. C. Chan,
J. M. Anderson,
L. C. Cantley
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.
Z. Songyang, J. Xu, L. C. Cantley, Division of Signal
Transduction, Beth Israel Hospital, and Department of Cell Biology,
Harvard Medical School, Boston, MA 02115, USA.
A. S. Fanning and J. M. Anderson, Departments of Internal Medicine and
Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
C. Fu and A. C. Chan, Howard Hughes Medical Institute, Center for
Immunology, Department of Medicine and Pathology, Washington University
School of Medicine, St. Louis, MO 63110, USA.
S. M. Marfatia and A. H. Chishti, Laboratory of Tumor Cell Biology,
Department of Biomedical Research, St. Elizabeth's Medical Center,
Tufts University, Boston, MA 02135, USA.
A. Crompton, ONYX Pharmaceuticals, 3031 Research Drive, Building
A, Richmond, CA 94806, USA.
*
To whom correspondence should be addressed. Present address:
68-380, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
