Title
Effect of membrane-mimicking environment on the interactions of Cu2+ with amyloidogenic fragment of chicken Prion protein
Author
Aleksandra Hecel, Sara Draghi, Daniela Valensin, Henryk Kozlowski
Year
2017
Journal
Dalton Transactions
Abstract
Prion Proteins (PrP) from different species have the ability to tightly bind Cu2+ ions. Copper coordination sites are located at the disordered and flexible N-terminal region which contains several His anchoring sites. Among them, two His residues are found in the so called amyloidogenic PrP region which is believed to play a key role in the process leading to oligomer and fibril formation. Both chicken and human amyloidogenic regions have a hydrofobic C-terminal region rich in Ala and Val amino acids. Recent findings revealed that this domain undergoes to random coil to α-helix structuring upon interaction with membrane models. This interaction might strongly impact metal binding abilities either in terms of donors set and affinity. In this study we investigated Cu2+ interaction with an amyloidogenig fragment, chPrP105-140, derived from chicken prion (chPrP), in different solution enviroments. The behavior of the peptide and its metal complexes was analyzed in water and in presence of negative and positived charged membrane mimicking enviroments formed by sodium dodecyl sulfate (SDS) and dodecyl trimethyl ammonium chloride (DTAC) micelles. The metal coordination sphere, the metal binding affinity and stechiometry was evaluated by combining spectroscopic and potentiometric methods. Finally we compare copper(II) interactions with human and chicken fragments. Our results indicate that the chicken fragment is a stronger copper ligan than human.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Coordination chemistry, Vesicle interactions, Biochemistry