ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P67. Interaction of Cu(II) Ions and Neurotoxic Fragment of Chicken Prion
Peptide
E. Gralka, a D. Valensin, b G. Valensin, b W. Kamysz, c H. Kozłowski a
a
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław,
Poland
e-mail: ewagral@wcheto.chem.uni.wroc.pl
b
Dipartimento di Chimica, Università di Siena, Siena, Italia
c Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
Prion proteins are a group of pathogenic glycoproteins which have several characteristic features:
a highly helical and ordered C-terminal domain, a disordered
N-terminal domain composed of multiple repeat units and hydrophobic neurotoxin fragment. Residue 106-126
has been shown to be highly fibrillogenic, resistant to proteinase K and toxic to neurons [1].
Recent studies brings evidence that prion proteins (PrP) are involved in the Cu(II) metabolism. In contrast to
mammalian PrP avian prion proteins have a considerably different N-terminal copper binding region and most
interestingly they are not able to undergo the conversion proces into an infectious isoform.
The unstructured region between the N-terminal domain and the structured C-terminal domain may play an
important role in amyloid formation and infectivity in prion desises. A presence of Cu(II) ions could have
profound implication in the structure of this PrP region.
There are secondary and tetriary structural similarity in the C-terminal domain between mammalian (hPrP) and
avian (chPrP) prion proteins dispite the low overall sequence identity (30%).The affinity, selectivity and Cu(II)
coordination of the hPrP and chPrP repeat domain are now well determine[2].
Definitely less information is available about coordination ability of the region called fifth Cu(II) binding site,
i.e. a fragment comprising His96, His111 in hPrP and His110, His 124 in chPrP. The affinity of His96 and
His111 for Cu(II) is similar to each other, although His111 seems to display higher affinity to metal ions [3].
Coordination of Cu(II) ions to chPrP peptides is not yet well established [4].
The aim of this study is to obtain speciation, affinity, bonding details and conformational features of chPrP
Cu(II) complexes.
References:
[1] B. Belosi, E. Gaggelli, R. Guerrini, H. Kozłowski, M. Łuczkowski, F.M. Mancini, M. Remelli,
D. Valensin, G. Valensin. ChemBioChem 2004, 349-359
[2] P.Stańczak, M. Łuczkowski, P. Juszczyk, Z. Grzonka, H. Kozłowski. Dalton. Trans. 2004, 2102-2107
[3] P. Davis, D. R. Brown, Biochem. J. 2008, 237-244
[4] G. Di Natale, G. Grasso, G. Impellizzeri, D. La Mendola, G.Micera, N. Mihala, Z. Nagy, K. Osz,
G. Pappalardo, V. Rigo, E. Rizzarelli, D. Sanna, I. Sovago. Inorg. Chem, 44, 2005, 7214-7225.
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