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

Indra Adi Lim, Duane D. Hall, Johannes W Hell

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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 (P0) 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 P0 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 I and protein kinase Cα, co-immunoprecipitated with PSD-95 and SAP102 from rat brain extracts.

Original languageEnglish (US)
Pages (from-to)21697-21711
Number of pages15
JournalJournal of Biological Chemistry
Volume277
Issue number24
DOIs
StatePublished - Jun 14 2002
Externally publishedYes

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PDZ Domains
Synapses
Valine
Threonine
Serine
Brain
Proteins
Angiogenesis Inhibitors
Isoleucine
Consensus Sequence
Glutamate Receptors
Human Genome
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Glutamine
Leucine
Protein Kinase C
Rats
Glutamic Acid
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. / Lim, Indra Adi; Hall, Duane D.; Hell, Johannes W.

In: Journal of Biological Chemistry, Vol. 277, No. 24, 14.06.2002, p. 21697-21711.

Research output: Contribution to journalArticle

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