Wydział Chemii

Caterina Migliorini

Adalgisa Sinicropi

Henryk Kozłowski

Marek Łuczkowski

Daniela Valensin

2014

Journal of Biological Inorganic Chemistry

19

635-645

10.1007/s00775-014-1132-7

Naukowa

Angielski

Artykuł

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 frag-ment of N-terminal domain of the protein spanning resi-dues 91–127 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) seques-tration by 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

Prion protein, Copper, His-111, Amyloidogenic region, ß-sheet

http://dx.doi.org/10.1007/s00775-014-1132-7

http://link.springer.com