title: Copper-binding activity of Trefoil factor 1 (TFF1): a new perspective in the study of the multifunctional roles of TFFs.
abstract: Trefoil factors (TFFs) are gastrointestinal peptides playing an essential role in the epithelial restitution. Among the three known TFF peptides, TFF1 is characterized by three disulfide bonds producing a compact globular structure and an extended and disordered tail formed by amino- and carboxy-termini. The presence of a cysteine surrounded by several negatively charged residues in this region of the protein, highly conserved in different species, suggests the possible formation of a metal-binding site. Affinity chromatography and mass spectrometric analyses allowed us to demonstrate a selective binding affinity of TFF1 for copper. The binding induces conformational changes in the tertiary structure as demonstrated by circular dichroism experiments, while limited proteolysis revealed an altered access to the cleavage sites in the amino- and carboxy-termini. The results of this study reveal a new property of TFF1 and suggest that copper could influence its biological activities by interfering with the dimerization of the peptide and/or the interaction with mucins or putative TFF receptors.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano, SA, Italy. tosco@unisa.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tosco
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Monti
authors.forename: Bianca
authors.initials: B
authors.lastname: Fontanella
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rio
authors.forename: Luigi
authors.initials: L
authors.lastname: Gomez-Paloma
authors.forename: Arturo
authors.initials: A
authors.lastname: Leone
authors.forename: Liberato
authors.initials: L
authors.lastname: Marzullo
mesh_terms: D001665:Binding Sites; D002846:Chromatography, Affinity; D003300:Copper / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D003300:Copper