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Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem

Nature Structural & Molecular Biologyvolume 12pages722728 (2005) | Download Citation



Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conserved C-terminal tail of X11α folds back and inserts into the target-binding groove of the first PDZ domain. The binding of this tail occludes the binding of other target peptides. This autoinhibited conformation of X11 requires that the two PDZ domains and the entire C-terminal tail be covalently connected to form an integral structural unit. The autoinhibited conformation of the X11 PDZ tandem provides a mechanistic explanation for the unique target-binding properties of the protein and hints at potential regulatory mechanisms for the X11–target interactions.

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This work was supported by grants CERG and AOE/B-15/01 from the University Grants Committee of Hong Kong to N.Y.I., J.X. and M.Z. The NMR spectrometer used in this work was purchased with funds donated to the Biotechnology Research Institute by the Hong Kong Jockey Club. M.Z. and N.Y.I. were recipients of the Croucher Foundation Senior Research Fellowship. We thank H. Zheng for the presenilin expression construct.

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Author notes

  1. Jia-Fu Long and Wei Feng: These authors contributed equally to this work.


  1. Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    • Jia-Fu Long
    • , Wei Feng
    • , Rui Wang
    • , Ling-Nga Chan
    • , Fanny C F Ip
    • , Jun Xia
    • , Nancy Y Ip
    •  & Mingjie Zhang


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The authors declare no competing financial interests.

Corresponding author

Correspondence to Mingjie Zhang.

Supplementary information

  1. Supplementary Fig. 1

    Comparisons of the conformation of various PDZ domains using the chemical shift perturbation approach. (PDF 83 kb)

  2. Supplementary Fig. 2

    Structures of the X11 PDZ domains determined by NMR spectroscopy. (PDF 716 kb)

  3. Supplementary Fig. 3

    Interaction of N-type calcium channel peptide with PDZ1. (PDF 181 kb)

  4. Supplementary Table 1

    Structural statistics for the family of 20 structures of PDZ1, PDZ1 in complex with the C-peptide, and PDZ2. (PDF 65 kb)

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