Tryptophan scanning analysis of the membrane domain of CTR-copper transporters

Christopher J. De Feo, Sara Mootien, Vinzenz M. Unger

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Membrane proteins of the CTR family mediate cellular copper uptake in all eukaryotic cells and have been shown to participate in uptake of platinum-based anticancer drugs. Despite their importance for life and the clinical treatment of malignancies, directed biochemical studies of CTR proteins have been difficult because high-resolution structural information is missing. Building on our recent 7Å structure of the human copper transporter hCTR1, we present the results of an extensive tryptophan-scanning analysis of hCTR1 and its distant relative, yeast CTR3. The comparative analysis supports our previous assignment of the transmembrane helices and shows that most functionally and structurally important residues are clustered around the threefold axis of CTR trimers or engage in helix packing interactions. The scan also identified residues that may play roles in interactions between CTR trimers and suggested that the first transmembrane helix serves as an adaptor that allows evolutionarily diverse CTRs to adopt the same overall structure. Together with previous biochemical and biophysical data, the results of the tryptophan scan are consistent with a mechanistic model in which copper transport occurs along the center of the trimer.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalJournal of Membrane Biology
Issue number2
StatePublished - Apr 2010


  • Biophysical techniques in membrane research
  • Membrane transport
  • Molecular structure of membrane transporters
  • Protein biochemistry
  • Structure and function of transport proteins

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology


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