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A structural perspective on copper uptake in eukaryotes

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Abstract

Over a decade ago, genetic studies identified a family of small integral membrane proteins, commonly referred to as copper transporters (CTRs) that are both required and sufficient for cellular copper uptake in a yeast genetic complementation assay. We recently used electron crystallography to determine a projection density map of the human high affinity transporter hCTR1 embedded into a lipid bilayer. At 6 Å resolution, this first glimpse of the structure revealed that hCTR1 is trimeric and possesses the type of radial symmetry that traditionally has been associated with the structure of certain ion channels such as potassium or gap junction channels. Representative for this particular type of architecture, a region of low protein density at the center of the trimer is consistent with the existence of a copper permeable pore along the center three-fold axis of the trimer. In this contribution, we will briefly discuss how recent structure–function studies correlate with the projection density map, and provide a perspective with respect to the cellular uptake of other transition metals.

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Acknowledgements

Ribbon diagrams were produced using the UCSF Chimera package from the Computer Graphics Laboratory, University of California, San Francisco (NIH P42 RR-01081). This work was funded by PHS grants GM07223 (CDF, SGA), NS56825 (CDF), NS45550 (SGA), and GM071590 (VMU).

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Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024, New Haven, CT, 06520-8024, USA

    Christopher J. De Feo & Vinzenz M. Unger

  2. Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, 92137, USA

    Stephen G. Aller

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  1. Christopher J. De Feo
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  2. Stephen G. Aller
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  3. Vinzenz M. Unger
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Correspondence to Vinzenz M. Unger.

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De Feo, C.J., Aller, S.G. & Unger, V.M. A structural perspective on copper uptake in eukaryotes. Biometals 20, 705–716 (2007). https://doi.org/10.1007/s10534-006-9054-7

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  • DOI: https://doi.org/10.1007/s10534-006-9054-7

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