Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the N-Terminus of Human Copper Transporter 1.

Journal Article (Journal Article)

Copper is a vital metal cofactor in enzymes that are essential to myriad biological processes. Cellular acquisition of copper is primarily accomplished through the Ctr family of plasma membrane copper transport proteins. Model peptide studies indicate that the human Ctr1 N-terminus binds to Cu(II) with high affinity through an amino terminal Cu(II), Ni(II) (ATCUN) binding site. Unlike typical ATCUN-type peptides, the Ctr1 peptide facilitates the ascorbate-dependent reduction of Cu(II) bound in its ATCUN site by virtue of an adjacent HH (bis-His) sequence in the peptide. It is likely that the Cu(I) coordination environment influences the redox behavior of Cu bound to this peptide; however, the identity and coordination geometry of the Cu(I) site has not been elucidated from previous work. Here, we show data from NMR, XAS, and structural modeling that sheds light on the identity of the Cu(I) binding site of a Ctr1 model peptide. The Cu(I) site includes the same bis-His site identified in previous work to facilitate ascorbate-dependent Cu(II) reduction. The data presented here are consistent with a rational mechanism by which Ctr1 provides coordination environments that facilitate Cu(II) reduction prior to Cu(I) transport.

Full Text

Duke Authors

Cited Authors

  • Pushie, MJ; Shaw, K; Franz, KJ; Shearer, J; Haas, KL

Published Date

  • September 2015

Published In

Volume / Issue

  • 54 / 17

Start / End Page

  • 8544 - 8551

PubMed ID

  • 26258435

Electronic International Standard Serial Number (EISSN)

  • 1520-510X

International Standard Serial Number (ISSN)

  • 0020-1669

Digital Object Identifier (DOI)

  • 10.1021/acs.inorgchem.5b01162


  • eng