Structure-function analyses of the ATX1 metallochaperone

Matthew E. Portnoy, Amy C. Rosenzweig, Tracey Rae, David L. Huffman, Thomas V. O'Halloran, Valeria Cizewski Culotta

Research output: Contribution to journalArticle

Abstract

Saccharomyces cerevisiae Atx1p represents a member of the family of metallochaperone molecules that escort copper to distinct intracellular targets. Atx1p specifically delivers copper to the Ccc2p copper transporter in the Golgi. Additionally, when overproduced, Atx1p substitutes for superoxide dismutase 1 in preventing oxidative damage; however the mechanistic overlap between these functions is unresolved. The crystal structure of Atx1p has been solved recently. By examining a surface electrostatic potential distribution, multiple conserved lysines are revealed on one face of Atx1p. An additional conserved lysine (Lys65) lies in close proximity to the metal binding site. Through site-directed mutagenesis, residues in the metal binding region including Lys65 were found to be necessary for both copper delivery to Ccc2p and for Atx1p antioxidant activity. Copper trafficking to Ccc2p also relied on the lysine-rich face of Atx1p. Surprisingly however, elimination of these lysines did not inhibit the antioxidant activity of Atx1p. We provide evidence that Atx1p does not suppress oxidative damage by a metallochaperone mechanism but may directly consume superoxide. Purified Cu-Atx1p reacts noncatalytically with superoxide anion in vitro. We conclude that the copper-trafficking and antioxidant functions of Atx1p arise from chemically and structurally distinct attributes of this metallochaperone.

Original languageEnglish (US)
Pages (from-to)15041-15045
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number21
DOIs
StatePublished - May 21 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Structure-function analyses of the ATX1 metallochaperone'. Together they form a unique fingerprint.

  • Cite this

    Portnoy, M. E., Rosenzweig, A. C., Rae, T., Huffman, D. L., O'Halloran, T. V., & Culotta, V. C. (1999). Structure-function analyses of the ATX1 metallochaperone. Journal of Biological Chemistry, 274(21), 15041-15045. https://doi.org/10.1074/jbc.274.21.15041