RGD Reference Report - Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. - Rat Genome Database

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Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102.

Authors: Lim, IA  Hall, DD  Hell, JW 
Citation: Lim IA, etal., J Biol Chem. 2002 Jun 14;277(24):21697-711. Epub 2002 Apr 5.
RGD ID: 8553393
Pubmed: PMID:11937501   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M112339200   (Journal Full-text)

PDZ domains typically interact with the very carboxyl terminus of their binding partners. Type 1 PDZ domains usually require valine, leucine, or isoleucine at the very COOH-terminal (P(0)) position, and serine or threonine 2 residues upstream at P(-2). We quantitatively defined the contributions of carboxyl-terminal residues to binding selectivity of the prototypic interactions of the PDZ domains of postsynaptic density protein 95 (PSD-95) and its homolog synapse-associated protein 90 (SAP102) with the NR2b subunit of the N-methyl-d-aspartate-type glutamate receptor. Our studies indicate that all of the last five residues of NR2b contribute to the binding selectivity. Prominent were a requirement for glutamate or glutamine at P(-3) and for valine at P(0) for high affinity binding and a preference for threonine over serine at P(-2), in the context of the last 11 residues of the NR2b COOH terminus. This analysis predicts a COOH-terminal (E/Q)(S/T)XV consensus sequence for the strongest binding to the first two PDZ domains of PSD-95 and SAP102. A search of the human genome sequences for proteins with a COOH-terminal (E/Q)(S/T)XV motif yielded 50 proteins, many of which have not been previously identified as PSD-95 or SAP102 binding partners. Two of these proteins, brain-specific angiogenesis inhibitor 1 and protein kinase Calpha, co-immunoprecipitated with PSD-95 and SAP102 from rat brain extracts.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Dlg3  (discs large MAGUK scaffold protein 3)
Dlg4  (discs large MAGUK scaffold protein 4)


Additional Information