The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP 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 the dimer [Cu(HGGG)]2 are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly’s is confirmed in the case of the Cu(HGGG) system. For the more interesting [Cu(HGGG)]2 dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.

Furlan, S., Guerrieri, F., La Penna, G., Morante, S., & Rossi, G.C. (2006). Ab initio simulations of Cu binding sites in the N-terminal region of PrPs, 34, 153-156.

Ab initio simulations of Cu binding sites in the N-terminal region of PrPs

MORANTE, SILVIA;ROSSI, GIANCARLO
2006

Abstract

The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP 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 the dimer [Cu(HGGG)]2 are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly’s is confirmed in the case of the Cu(HGGG) system. For the more interesting [Cu(HGGG)]2 dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.
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Rilevanza internazionale
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Sì, ma tipo non specificato
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
eng
Furlan, S., Guerrieri, F., La Penna, G., Morante, S., & Rossi, G.C. (2006). Ab initio simulations of Cu binding sites in the N-terminal region of PrPs, 34, 153-156.
Furlan, S; Guerrieri, F; La Penna, G; Morante, S; Rossi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/39454
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