The human prion protein binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH 7.4. Recent experiments have shown that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square-planar configuration. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the coordination of copper to the binding sites of the prion protein octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)(wat), Cu(HGGG), and [Cu(HGGG)](2) are presented. While the presence of a Trp residue and a water molecule does not seem to affect the nature of the copper coordination, high stability of the bond between copper and the amide nitrogen of deprotonated Gly residues is confirmed in all cases. For the more interesting [Cu(HGGG)](2) complex, a dynamically entangled arrangement of the two domains with exchange of amide nitrogen bonds between the two copper centers emerges, which is consistent with the short Cu-Cu distance observed in experiments at full copper occupancy.

Furlan, S., La Penna, G., Guerrieri, F., Morante, S., Rossi, G. (2007). Ab initio simulations of Cu binding sites on the N-terminal region of prion protein, 12(4), 571-583 [10.1007/s00775-007-0218-x].

Ab initio simulations of Cu binding sites on the N-terminal region of prion protein

MORANTE, SILVIA;ROSSI, GIANCARLO
2007-01-01

Abstract

The human prion protein binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH 7.4. Recent experiments have shown that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square-planar configuration. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the coordination of copper to the binding sites of the prion protein octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)(wat), Cu(HGGG), and [Cu(HGGG)](2) are presented. While the presence of a Trp residue and a water molecule does not seem to affect the nature of the copper coordination, high stability of the bond between copper and the amide nitrogen of deprotonated Gly residues is confirmed in all cases. For the more interesting [Cu(HGGG)](2) complex, a dynamically entangled arrangement of the two domains with exchange of amide nitrogen bonds between the two copper centers emerges, which is consistent with the short Cu-Cu distance observed in experiments at full copper occupancy.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA)
English
Ab initio molecular dynamics; Computer simulations; Copper; Prion protein
Furlan, S., La Penna, G., Guerrieri, F., Morante, S., Rossi, G. (2007). Ab initio simulations of Cu binding sites on the N-terminal region of prion protein, 12(4), 571-583 [10.1007/s00775-007-0218-x].
Furlan, S; La Penna, G; Guerrieri, F; Morante, S; Rossi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/37509
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