RSC Publishing


Publishing

 

Cover image for Dalton Transactions, select for current issue

Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



Subscribers

Non-subscribers

Free access



Paper

Dalton Trans., 2008, 5207 - 5219, DOI: 10.1039/b806192k

CuII binding sites located at His-96 and His-111 of the human prion protein: thermodynamic and spectroscopic studies on model peptides

Ewa Gralka, Daniela Valensin, Elena Porciatti, Carolina Gajda, Elena Gaggelli, Gianni Valensin, Wojciech Kamysz, Rafa Nadolny, Remo Guerrini, Dimitri Bacco, Maurizio Remelli and Henryk Kozlowski

The prion protein (PrP) is a Cu2+-binding cell-surface glycoprotein. Using PrP peptide fragments, by means of potentiometric, spectroscopic and thermodynamic techniques, we have shown that Cu2+ ions bind to the region comprising His-96, His-111 and the octarepeat domain within residues 60–91. Cu2+ may bind in different modes, which strongly depend both on His position within the peptide sequence and on the adjacent residues. We have used a series of protected oligopeptides having His at the C- or the N-terminus, inducing different binding modes to amide nitrogens around the His residue, either towards the N- or C-terminus. His imidazole acts as an anchoring site for Cu2+ and then binding to ionized amide nitrogens follows. When it is directed towards the C-terminus the formation of a less stable seven-membered chelate ring with a {Nim, N-} binding mode occurs. When coordination goes towards the N-terminus the thermodynamically more stable six-membered chelate ring is formed. NMR data suggest that both the coordination modes are possible for the model peptides; however, the thermodynamic measurements show that they only slightly differ in energy and the influence of the adjacent amino acid residues can address the coordination toward the C- or the N-terminus.

Graphical abstract image for this article (ID: b806192k)