Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ

Cell. 1996 Jun 28;85(7):1067-76. doi: 10.1016/s0092-8674(00)81307-0.


Modular PDZ domains, found in many cell junction-associated proteins, mediate the clustering of membrane ion channels by binding to their C-terminus. The X-ray crystallographic structures of the third PDZ domain from the synaptic protein PSD-95 in complex with and in the absence of its peptide ligand have been determined at 1.8 angstroms and 2.3 angstroms resolution, respectively. The structures reveal that a four-residue C-terminal stretch (X-Thr/Ser-X-Val-COO(-)) engages the PDZ domain through antiparallel main chain interactions with a beta sheet of the domain. Recognition of the terminal carboxylate group of the peptide is conferred by a cradle of main chain amides provided by a Gly-Leu-Gly-Phe loop as well as by an arginine side chain. Specific side chain interactions and a prominent hydrophobic pocket explain the selective recognition of the C-terminal consensus sequence.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography
  • Image Processing, Computer-Assisted
  • Membrane Proteins / chemistry*
  • Molecular Biology
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid


  • Membrane Proteins
  • Nerve Tissue Proteins
  • Peptides
  • postsynaptic density proteins