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|Title:||Copper-induced structural propensities of the amyloidogenic region of human prion protein||Authors:||Migliorini, C.
|Keywords:||Prion protein; Copper; His-111; Amyloidogenic region; beta-Sheet||Issue Date:||2014||Project:||None||Journal:||JBIC||Abstract:||
Transmissible spongiform encephalopathies areassociated with the misfolding of the cellular Prion Protein(PrPC) to an abnormal protein isoform, called scrapie prionprotein (PrPSc). The structural rearrangement of the fragmentof N-terminal domain of the protein spanning residues91–127 is critical for the observed structuraltransition. The amyloidogenic domain of the proteinencloses two copper-binding sites corresponding to His-96and His-111 residues that act as anchors for metal ionbinding. Previous studies have shown that Cu(II) sequestrationby both sites may modulate the peptide’s tendencyto aggregation as it inflicts the hairpin-like structure thatstabilizes the transition states leading to b-sheet formation.On the other hand, since both His sites differ in their abilityto Cu(II) sequestration, with His-111 as a preferred bindingsite, we found it interesting to test the role of Cu(II)coordination to this single site on the structural propertiesof amyloidogenic domain. The obtained results reveal thatcopper binding to His-111 site imposes precise backbonebending and weakens the natural tendency of apo peptideto b-sheet formation.
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