Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity |
| |
Authors: | Alessandra Tosco Maria Chiara Monti Bianca Fontanella Sandro Montefusco Luca D’Andrea Barbara Ziaco Daniela Baldantoni Marie-Christine Rio Liberato Marzullo |
| |
Institution: | 1. Division of Biomedicine “Arturo Leone”, Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo, 84084, Fisciano (SA), Italy 5. Division of Chemistry and Chemical Technologies “Luigi Gomez-Paloma”, Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo, 84084, Fisciano (SA), Italy 2. Institute of Biostructures and Bioimaging, CNR, Naples, Italy 3. Department of Chemistry, University of Salerno, Fisciano (SA), Italy 4. Department of Cancer Biology, Institute of Genetics and Molecular and Cellular Biology, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Strasbourg, France
|
| |
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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|