Abstract
The PDZ domain of neuronal nitric oxide synthase (nNOS) functions as a scaffold for organizing the signal transduction complex of the enzyme. The NMR structure of a complex composed of the nNOS PDZ domain and an associated peptide suggests that a two-stranded beta-sheet C-terminal to the canonical PDZ domain may mediate its interaction with the PDZ domains of postsynaptic density-95 and alpha-syntrophin. The structure also provides the molecular basis of recognition of Asp-X-Val-COOH peptides by the nNOS PDZ domain. The role of the C-terminal extension in Asp-X-Val-COOH peptide binding is investigated. Additionally, NMR studies further show that the Asp-X-Val-COOH peptide and a C-terminal peptide from a novel cytosolic protein named CAPON bind to the same pocket of the nNOS PDZ domain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Amino Acids / chemistry
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Amino Acids / metabolism
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Animals
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism
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Dimerization
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Models, Biological
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Models, Molecular
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Molecular Sequence Data
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Nitric Oxide Synthase / chemistry*
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type I
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Nuclear Magnetic Resonance, Biomolecular
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism*
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Rats
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / metabolism
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Melatonin
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Solutions
Substances
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Adaptor Proteins, Signal Transducing
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Amino Acids
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Carrier Proteins
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NOS1AP protein, rat
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Nos1ap protein, mouse
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Peptide Fragments
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Receptors, Melatonin
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Solutions
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat