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Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition

Nature Structural Biology volume 5, pages 317–325 (1998)Cite this article

Abstract

PDZ domain containing proteins assist formation of cell–cell junctions and localization of membrane protein receptors and ion channels. PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ domains fall into two classes. The first crystal structure of a class II PDZ domain, that of hCASK, has been solved by multi-wavelength anomalous dispersion phasing. Complex formation with the C-terminus of a neighboring non-crystallographically related PDZ domain reveals interactions between hCASK and its ligand. Class II PDZ domains differ from class I domains by formation of a second hydrophobic binding pocket. The C-terminal carboxylate binding loop of the PDZ domain is structurally conserved in both classes suggesting a generalized carboxylate binding motif (h–Gly–h) where h is a hydrophobic residue.

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Authors and Affiliations

  1. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 06520, USA

    Danette L. Daniels & Axel T. Brünger

  2. Departments of Internal Medicine and Cell Biology, Yale University School of Medicine, New Haven, Connecticut, 06520, USA

    Alexandra R. Cohen & James M. Anderson

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  1. Danette L. Daniels
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Correspondence to Axel T. Brünger.

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Daniels, D., Cohen, A., Anderson, J. et al. Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition. Nat Struct Mol Biol 5, 317–325 (1998). https://doi.org/10.1038/nsb0498-317

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