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PSD-95 Assembles a Ternary Complex with theN-Methyl-d-aspartic Acid Receptor and a Bivalent Neuronal NO Synthase PDZ Domain
Open accessAbstract
Nitric oxide (NO) biosynthesis in cerebellum is preferentially activated by calcium influx through N-methyl-D-aspartate (NMDA)-type glutamate receptors, suggesting that there is a specific link between these receptors and neuronal NO synthase (nNOS). Here, we find that PSD-95 assembles a postsynaptic protein complex containing nNOS and NMDA receptors. Formation of this complex is mediated by the PDZ domains of PSD-95, which bind to the COOH termini of specific NMDA receptor subunits. In contrast, nNOS is recruited to this complex by a novel PDZ-PDZ interaction in which PSD-95 recognizes an internal motif adjacent to the consensus nNOS PDZ domain. This internal motif is a structured "pseudo-peptide" extension of the nNOS PDZ that interacts with the peptide-binding pocket of PSD-95 PDZ2. This asymmetric interaction leaves the peptide-binding pocket of the nNOS PDZ domain available to interact with additional COOH-terminal PDZ ligands. Accordingly, we find that the nNOS PDZ domain can bind PSD-95 PDZ2 and a COOH-terminal peptide simultaneously. This bivalent nature of the nNOS PDZ domain further expands the scope for assembly of protein networks by PDZ domains.
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Cites
Competitive binding of α-actinin and calmodulin to the NMDA receptor
Wyszynski, M., Lin, J., Rao, A., Nigh, E., Beggs, A. H., Craig, A. M., & Sheng, M. (1997) · Nature · doi:10.1038/385439a0 · Cited by 596
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Cited by
Nitric oxide synthases: structure, function and inhibition
ALDERTON, W. K., COOPER, C. E., & KNOWLES, R. G. (2001) · Biochemical Journal · doi:10.1042/bj3570593 · Cited by 4,110
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions
Qin, C., Yang, S., Chu, Y.-H., Zhang, H., Pang, X.-W., Chen, L., Zhou, L.-Q., Chen, M., Tian, D.-S., & Wang, W. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01064-1 · Cited by 939
Effects of environmental enrichment on gene expression in the brain
Rampon, C., Jiang, C. H., Dong, H., Tang, Y.-P., Lockhart, D. J., Schultz, P. G., Tsien, J. Z., & Hu, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12880 · Cited by 615
Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012484 · Cited by 598
Metadata
- Authors
- Christopherson, K. S., Hillier, B. J., Lim, W. A., & Bredt, D. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 274
- Issue
- 39
- Pages
- 27467-27473
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2162611266
- Cited by
- 540
- References
- 3
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: PSD-95 Assembles a Ternary Complex with theN-Methyl-d-aspartic Acid Receptor and a Bivalent Neuronal NO Synthase PDZ Domain. https://app.cochat.ai/papers/10.1074/jbc.274.39.27467
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- Christopherson, K. S., Hillier, B. J., Lim, W. A., & Bredt, D. S. (1999). PSD-95 Assembles a Ternary Complex with theN-Methyl-d-aspartic Acid Receptor and a Bivalent Neuronal NO Synthase PDZ Domain. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.39.27467
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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