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Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase

Nature Structural Biology volume 5, pages 47–54 (1998)Cite this article

Abstract

Menkes disease is an X-linked disorder in copper transport that results in death during early childhood. The solution structures of both apo and Ag(l)-bound forms of the fourth metal-binding domain (mbd4) from the Menkes copper-transporting ATPase have been solved. The 72-residue mbd4 has a ferredoxin-like βαββαβ fold. Structural differences between the two forms are limited to the metal-binding loop, which is disordered in the apo structure but well ordered in the Ag(l)-bound structure. Ag(l) binds in a linear bicoordinate manner to the two Cys residues of the conserved GMTCxxC motif; Cu(l) likely coordinates in a similar manner. Menkes mbd4 is thus the first bicoordinate copper-binding protein to be characterized structurally. Sequence comparisons with other heavy-metal-binding domains reveal a conserved hydrophobic core and metal-binding motif.

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Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute and Departments of Medicine and Pediatrics, University of California, San Francisco, California, 94143, USA

    Jane Gitschier

  2. Department of Protein Chemistry, Genentech, Inc., South San Francisco, California, 90480, USA

    Barbara Moffat

  3. Department of Cell Culture, Genentech, Inc., South San Francisco, California, 90480, USA

    Dorothea Reilly

  4. Department of Molecular Biology, Genentech, Inc., South San Francisco, California, 90480, USA

    William I. Wood

  5. Department of Protein Engineering, Genentech, Inc., South San Francisco, California, 90480, USA

    Wayne J. Fairbrother

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  3. Dorothea Reilly
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Gitschier, J., Moffat, B., Reilly, D. et al. Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase. Nat Struct Mol Biol 5, 47–54 (1998). https://doi.org/10.1038/nsb0198-47

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