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

doi:10.1074/jbc.M112339200

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

Journal article

Open access

Peer reviewed

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

Indra Adi Lim, Duane D Hall and Johannes W Hell

The Journal of biological chemistry, Vol.277(24), pp.21697-21711

06/14/2002

DOI: 10.1074/jbc.M112339200

PMID: 11937501

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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 (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.

Disks Large Homolog 4 Protein

Threonine - chemistry

Humans

Molecular Sequence Data

Receptors, Neurotransmitter - chemistry

Immunoblotting

Isoenzymes - chemistry

Recombinant Fusion Proteins - metabolism

Brain - metabolism

Dose-Response Relationship, Drug

Nerve Tissue Proteins - chemistry

Protein Kinase C-alpha

Angiogenic Proteins

Frizzled Receptors

Protein Structure, Tertiary

Amino Acid Sequence

Peptides - chemistry

Receptors, G-Protein-Coupled

Glutathione Transferase - metabolism

Intracellular Signaling Peptides and Proteins

Models, Molecular

Rats

Spectrometry, Fluorescence

Serine - chemistry

Angiogenesis Inhibitors

Precipitin Tests

Nuclear Proteins

Membrane Proteins

Sequence Homology, Amino Acid

Animals

Anisotropy

Protein Kinase C - chemistry

Protein Binding

Transcription Factors

Kinetics

Proteins - chemistry

Genome, Human

Neuropeptides - chemistry

Details

Title: Subtitle: Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102
Creators: Indra Adi Lim - Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706-1532, USA
Duane D Hall
Johannes W Hell
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(24), pp.21697-21711
DOI: 10.1074/jbc.M112339200
PMID: 11937501
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: R01-NS35563 / NINDS NIH HHS AG00213 / NIA NIH HHS DK07759 / NIDDK NIH HHS
Language: English
Date published: 06/14/2002
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094490802771

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