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Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1.

Publication ,  Journal Article
Schulte, NB; Pushie, MJ; Martinez, A; Sendzik, M; Escobedo, M; Kuter, K; Haas, KL
Published in: Inorganic chemistry
March 2023

Human serum albumin (HSA) is the major copper (Cu) carrier in blood. The majority of previous studies that have investigated Cu interactions with HSA have focused primarily on the Cu(II) oxidation state. Yet, cellular Cu uptake by the human copper transport protein (Ctr1), a plasma membrane-embedded protein responsible for Cu uptake into cells, requires Cu(I). Recent in vitro work has determined that reducing agents, such as the ascorbate present in blood, are sufficient to reduce the Cu(II)HSA complex to form Cu(I)HSA and that Cu(I) is bound to HSA with pM affinity. The biological accessibility of Cu(I)HSA suggests that HSA-bound Cu(I) may be an unappreciated form of Cu cargo and a key player in extracellular Cu trafficking. To better understand Cu trafficking by HSA, we sought to investigate the exchange of Cu(I) from HSA to a model peptide of the Cu-binding ectodomain of Ctr1. In this study, we used X-ray absorption near-edge spectroscopy to show that Cu(I) becomes more highly coordinated as increasing amounts of the Ctr1-14 model peptide are added to a solution of Cu(I)HSA. Extended X-ray absorption fine structure (EXAFS) spectroscopy was used to further characterize the interaction of Cu(I)HSA with Ctr1-14 by determining the ligands coordinating Cu(I) and their bond lengths. The EXAFS data support that some Cu(I) likely undergoes complete transfer from HSA to Ctr1-14. This finding of HSA interacting with and releasing Cu(I) to an ectodomain model peptide of Ctr1 suggests a mechanism by which HSA delivers Cu(I) to cells under physiological conditions.

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Published In

Inorganic chemistry

DOI

EISSN

1520-510X

ISSN

0020-1669

Publication Date

March 2023

Volume

62

Issue

10

Start / End Page

4021 / 4034

Related Subject Headings

  • Serum Albumin, Human
  • Serum Albumin
  • Peptides
  • Oxidation-Reduction
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper
  • Biological Transport
  • 3403 Macromolecular and materials chemistry
  • 3402 Inorganic chemistry
 

Citation

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Schulte, N. B., Pushie, M. J., Martinez, A., Sendzik, M., Escobedo, M., Kuter, K., & Haas, K. L. (2023). Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1. Inorganic Chemistry, 62(10), 4021–4034. https://doi.org/10.1021/acs.inorgchem.2c03753
Schulte, Natalie B., M Jake Pushie, Ana Martinez, Madison Sendzik, Maria Escobedo, Kristin Kuter, and Kathryn L. Haas. “Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1.Inorganic Chemistry 62, no. 10 (March 2023): 4021–34. https://doi.org/10.1021/acs.inorgchem.2c03753.
Schulte NB, Pushie MJ, Martinez A, Sendzik M, Escobedo M, Kuter K, et al. Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1. Inorganic chemistry. 2023 Mar;62(10):4021–34.
Schulte, Natalie B., et al. “Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1.Inorganic Chemistry, vol. 62, no. 10, Mar. 2023, pp. 4021–34. Epmc, doi:10.1021/acs.inorgchem.2c03753.
Schulte NB, Pushie MJ, Martinez A, Sendzik M, Escobedo M, Kuter K, Haas KL. Exploration of the Potential Role of Serum Albumin in the Delivery of Cu(I) to Ctr1. Inorganic chemistry. 2023 Mar;62(10):4021–4034.
Journal cover image

Published In

Inorganic chemistry

DOI

EISSN

1520-510X

ISSN

0020-1669

Publication Date

March 2023

Volume

62

Issue

10

Start / End Page

4021 / 4034

Related Subject Headings

  • Serum Albumin, Human
  • Serum Albumin
  • Peptides
  • Oxidation-Reduction
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper
  • Biological Transport
  • 3403 Macromolecular and materials chemistry
  • 3402 Inorganic chemistry