Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity - Archive ouverte HAL Access content directly
Journal Articles Cellular and Molecular Life Sciences Year : 2010

Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity

Alessandra Tosco
  • Function : Author
Maria Chiara Monti
  • Function : Author
Bianca Fontanella
  • Function : Author
Sandro Montefusco
  • Function : Author
Luca d'Andrea
  • Function : Author
Barbara Ziaco
  • Function : Author
Daniela Baldantoni
  • Function : Author
Liberato Marzullo
  • Function : Author

Abstract

Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility, and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses. We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper. Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression and invasion.

Dates and versions

hal-04014321 , version 1 (03-03-2023)

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Alessandra Tosco, Maria Chiara Monti, Bianca Fontanella, Sandro Montefusco, Luca d'Andrea, et al.. Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity. Cellular and Molecular Life Sciences, 2010, 67 (11), pp.1943-1955. ⟨10.1007/s00018-010-0309-7⟩. ⟨hal-04014321⟩
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