Solution structure of the extended neuronal nitric oxide synthase PDZ domain complexed with an associated peptide

The PDZ domain of neuronal nitric oxide synthase (nNOS) functions as a scaf fold for organizing the signal transduction complex of the enzyme. The NMR structure of a complex composed of the nNOS PDZ domain and an associated pe ptide suggests that a two-stranded beta-sheet C-terminal to the canonical P DZ 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 inve stigated. Additionally, NMR studies further show that the Asp-X-Val-COOH pe ptide and a C-terminal peptide from a novel cytosolic protein named CAPON b ind to the same pocket of the nNOS PDZ domain.