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Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2.

Publication ,  Journal Article
Schwab, S; Shearer, J; Conklin, SE; Alies, B; Haas, KL
Published in: Journal of inorganic biochemistry
May 2016

The critical nature of the copper transporter 1 (Ctr1) in human health has spurred investigation of Ctr1 structure and function. Ctr1 specifically transports Cu(I), the reduced form of copper, across the plasma membrane. Thus, extracellular Cu(II) must be reduced prior to transport. Unlike yeast Ctr1, mammalian Ctr1 does not rely on any known mammalian reductase. Previous spectroscopic studies of model peptides indicate that human Ctr1 could serve as both copper reductase and transporter. Ctr1 peptides bind Cu(II) at an amino terminal high-affinity Cu(II), Ni(II) ATCUN site. Ascorbate-dependent reduction of the Cu(II)-ATCUN complex is possible by virtue of an adjacent HH (bis-His), as this bis-His motif and one methionine ligand constitute a high affinity Ctr1 Cu(I) binding site. Here, we synthetically varied the distance between the ATCUN and bis-His motifs in a series of peptides based on the human Ctr1 amino terminal, with the general sequence MDHAnHHMGMSYMDS, where n=0-4. We tested the ability of each peptide to reduce Cu(II) with ascorbate and stabilize Cu(I) under ambient conditions (20% O2). This study reveals that significant differences in coordination structure and chemical behavior with ascorbate and O2 result from changes in the sequence proximity of ATCUN and bis-His. Peptides that deviate from the native Ctr1 pattern were less effective at forming stable Cu(I)-peptide complexes and/or resulted in O2-dependent oxidative damage to the peptide.

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Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

May 2016

Volume

158

Start / End Page

70 / 76

Related Subject Headings

  • Peptides
  • Oxygen
  • Oxidation-Reduction
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper Transporter 1
  • Copper
  • Cation Transport Proteins
  • Binding Sites
  • Ascorbic Acid
 

Citation

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Schwab, S., Shearer, J., Conklin, S. E., Alies, B., & Haas, K. L. (2016). Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2. Journal of Inorganic Biochemistry, 158, 70–76. https://doi.org/10.1016/j.jinorgbio.2015.12.021
Schwab, Stefanie, Jason Shearer, Steven E. Conklin, Bruno Alies, and Kathryn L. Haas. “Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2.Journal of Inorganic Biochemistry 158 (May 2016): 70–76. https://doi.org/10.1016/j.jinorgbio.2015.12.021.
Schwab S, Shearer J, Conklin SE, Alies B, Haas KL. Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2. Journal of inorganic biochemistry. 2016 May;158:70–6.
Schwab, Stefanie, et al. “Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2.Journal of Inorganic Biochemistry, vol. 158, May 2016, pp. 70–76. Epmc, doi:10.1016/j.jinorgbio.2015.12.021.
Schwab S, Shearer J, Conklin SE, Alies B, Haas KL. Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2. Journal of inorganic biochemistry. 2016 May;158:70–76.
Journal cover image

Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

May 2016

Volume

158

Start / End Page

70 / 76

Related Subject Headings

  • Peptides
  • Oxygen
  • Oxidation-Reduction
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper Transporter 1
  • Copper
  • Cation Transport Proteins
  • Binding Sites
  • Ascorbic Acid