CNR ExploRA

Articolo in rivista, 2020, ENG, 10.3390/ijms21249343

The Role of Copper (II) on Kininogen Binding to Tropomyosin in the Presence of a Histidine-Proline-Rich Peptide

Santoro, Anna Maria; Zimbone, Stefania; Magri, Antonio; La Mendola, Diego; Grasso, Giulia

CNR Ist Cristallografia Sede Secondaria Catania; Univ Pisa

The antiangiogenic activity of the H/P domain of histidine-proline-rich glycoprotein is mediated by its binding with tropomyosin, a protein exposed on endothelial cell-surface during the angiogenic switch, in presence of zinc ions. Although it is known that copper ion serum concentration is significantly increased in cancer patients, its role in the interaction of H/P domain with tropomyosin, has not yet been studied. In this paper, by using ELISA assay, we determined the modulating effect of TetraHPRG peptide, a sequence of 20 aa belonging to H/P domain, on the binding of Kininogen (HKa) with tropomyosin, both in absence and presence of copper and zinc ions. A potentiometric study was carried out to characterize the binding mode adopted by metal ions with TetraHPRG, showing the formation of complex species involving imidazole amide nitrogen atoms in metal binding. Moreover, circular dichroism showed a conformational modification of ternary systems formed by TetraHPRG, HKa and copper or zinc. Interestingly, slight pH variation influenced the HKa-TetraHPRG-tropomyosin binding. All these results indicate that both metal ions are crucial in the interaction between TetraHPRG, tropomyosin and HKa.

International journal of molecular sciences (Print) 21 (24)