Formation of a native-like beta-hairpin finger structure of a peptide fromthe extended PDZ domain of neuronal nitric oxide synthase in aqueous solution

Neuronal nitric oxide synthase (nNOS) is targeted to the cell membrane via interactions of its extended PDZ domain with PDZ domains of membrane-associ ated proteins including PSD-95 and alpha 1-syntrophin. The formation of het erodimers between the nNOS PDZ domain and the PDZ domains of nNOS-binding p roteins requires a stretch of continuous amino-acid residues C-terminal to the canonical nNOS PDZ domain. In this work, we show that a 27-residue pept ide comprising the C-terminal extension of the extended nNOS PDZ domain is capable of binding to PSD-95. The structure of the 27-residue peptide in aq ueous solution was determined using multidimensional NMR-spectroscopic tech niques. The free peptide adopts a native-like beta-hairpin finger structure in aqueous solution. The results indicate that the C-terminal extension pe ptide of the nNOS PDZ domain may represent a relatively independent structu ral unit in the mediation of the interaction between nNOS and PDZ domain-co ntaining proteins including PSD-95 and alpha 1-syntrophin.