Electronic properties of a PrP-Cu(ii) complex as a marker of 5-fold Cu(ii) coordination.

Human prion protein is a subject of extensive study, related in particular to the molecular basis of neurodegenerative disease development and prevention. This protein has two main domains: the membrane C-terminal, structured domain as well as the unstructured N-terminal domain. While PrPC (23-231) has up to eight Cu(ii) binding sites in the N-terminal domain, it includes a characteristic, conservative octarepeat region PHGGGWGQ, which was studied by means of X-ray absorption near edge spectroscopy. The measurements were conducted at the SuperXAS beamline (SLS, PSI, Villigen). For the initial 1 : 1 protein-to-Cu(ii) ratio, the two main Cu(ii) binding modes were identified using linear combination fitting and ab initio FEFF calculations for X-ray spectra. Their electronic structures indicated that Cu(ii) coordinated by strong π-donors could effectively suppress the pre-edge structure due to the filling of empty Cu(ii) d-states. The suppression was correlated with the charge transfer effect and filling of the virtual electronic Cu(ii) states. What is more, we showed that the 1s → 4p + LMCT (Ligand-to-Metal-Charge-Transfer) multielectron transition relation with the main edge transition could be used as a marker for preliminary comparison of an unknown organic compound to a reference. The presented results permitted a possible explanation of the mechanism of choosing the preferred Cu(ii) modes in PrPC-Cu(ii) coordination processes and of the complex stability from the electronic point of view.