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

Nature Structural Biology volume 6, pages 417–421 (1999)Cite this article

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 β-sheet C-terminal to the canonical PDZ domain may mediate its interaction with the PDZ domains of postsynaptic density-95 and α-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.

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Figure 1: a, Stereoview showing the best-fit superposition of the backbone atoms (N, Cα, and C') of the final 15 structures of the nNOS PDZ–MelR peptide complex.
Figure 2: a, Stereoview atom representation of the MelR peptide binding pocket of nNOS PDZ.
Figure 3: a, Plot of combined 1H and 15N chemical shift differences of the extended and canonical lengths of nNOS PDZ complexed with the MelR peptide.
Figure 4: Model for nNOS signal transduction complex organization by PDZ domains.

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Acknowledgements

We thank L. E. Kay for providing NMR pulse sequences, R. Muhandiram for help with the NMR experiments, D. Bredt for communicating unpublished experimental results, and D. Miller-Martini for critical reading and comments on the manuscript. This research was supported by the RGC grants from the Research Grant Council of Hong Kong. The NMR spectrometer used in this work was purchased by the Biotechnology Research Institute of HKUST.

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  1. Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China

    Hidehito Tochio, Qiang Zhang, Pravat Mandal, Ming Li & Mingjie Zhang

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Tochio, H., Zhang, Q., Mandal, P. et al. Solution structure of the extended neuronal nitric oxide synthase PDZ domain complexed with an associated peptide. Nat Struct Mol Biol 6, 417–421 (1999). https://doi.org/10.1038/8216

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