Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95

Neuron. 1997 May;18(5):803-14. doi: 10.1016/s0896-6273(00)80319-0.


The PSD-95/SAP90 family of PDZ-containing proteins is directly involved in the clustering of specific ion channels at synapses. We report that channel clustering depends on a conserved N-terminal domain of PSD-95 that mediates multimerization and disulfide linkage of PSD-95 protomers. This N-terminal multimerization domain confers channel clustering activity on a single PDZ domain. Thus, channel clustering depends on aggregation of PDZ domains achieved by head-to-head multimerization of PSD-95, rather than by concatenation of PDZ domains in PSD-95 monomers. This mechanism predicts that PSD-95 can organize heterogeneous membrane protein clusters via differential binding specificities of its three PDZ domains. PSD-95 and its relative chapsyn-110 exist as disulfide-linked complexes in rat brain, consistent with head-to-head multimerization of these proteins in vivo.

MeSH terms

  • Animals
  • COS Cells / chemistry
  • COS Cells / physiology
  • Cross-Linking Reagents / chemistry
  • Cross-Linking Reagents / metabolism
  • Disks Large Homolog 4 Protein
  • Disulfides / chemistry*
  • Disulfides / metabolism
  • Gene Deletion
  • Guanylate Kinases
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Nucleoside-Phosphate Kinase / genetics
  • Nucleoside-Phosphate Kinase / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / metabolism*
  • Precipitin Tests
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Rats
  • Sequence Homology, Amino Acid
  • Shaker Superfamily of Potassium Channels
  • Transfection
  • Tumor Suppressor Proteins


  • Cross-Linking Reagents
  • Disks Large Homolog 4 Protein
  • Disulfides
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Mpp2 protein, rat
  • Nerve Tissue Proteins
  • Potassium Channels
  • Shaker Superfamily of Potassium Channels
  • Tumor Suppressor Proteins
  • postsynaptic density proteins
  • Nucleoside-Phosphate Kinase
  • DLG2 protein, human
  • Guanylate Kinases