Unbound position II in MXCXXC metallochaperone model peptides impacts metal binding mode and reactivity: Distinct similarities to whole proteins

Michal S. Shoshan, Noa Dekel, Wojciech Goch, Deborah E. Shalev, Tsafi Danieli, Mario Lebendiker, Wojciech Bal, Edit Y. Tshuva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I)-Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid oxidation of its complex; in contrast, the Thr peptide with the Cys-Cu(I)-Met coordination under neutral conditions demonstrated weaker and pH dependent binding. Studies with human antioxidant protein 1 (Atox1) and three of its mutants where S residues were replaced with Ala suggested that (a) the binding affinity is influenced more by the binding sequence than by the protein fold (b) pH may play a role in binding reactivity, and (c) mutating the Met impacted the affinity and oxidation rate more drastically than did mutating one of the Cys, supporting its important role in protein function. Position II thus plays a dominant role in metal binding and transport.

Original languageAmerican English
Pages (from-to)29-36
Number of pages8
JournalJournal of Inorganic Biochemistry
Volume159
DOIs
StatePublished - Jun 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.

Keywords

  • Atox1
  • Cu
  • Metalloproteins
  • NMR
  • Peptides

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