Please use this identifier to cite or link to this item:
Title: Remote His50 Acts as a Coordination Switch in the High-Affinity N-Terminal Centered Copper(II) Site of α-Synuclein
Authors: De Ricco, R.
Valensin, Daniela 
Dell'Acqua, S.
Casella, L.
Dorlet, P.
Faller, P.
Hureau, C.
Issue Date: 2015
Project: None 
Parkinson's disease (PD) etiology is closely linked to the aggregation of α-synuclein (αS). Copper(II) ions can bind to αS and may impact its aggregation propensity. As a consequence, deciphering the exact mode of Cu(II) binding to αS is important in the PD context. Several previous reports have shown some discrepancies in the description of the main Cu(II) site in αS, which are resolved here by a new scenario. Three Cu(II) species can be encountered, depending on the pH and the Cu:αS ratio. At low pH, Cu(II) is bound to the N-terminal part of the protein by the N-terminal amine, the adjacent deprotonated amide group of the Asp2 residue, and the carboxylate group from the side chain of the same Asp2. At pH 7.4, the imidazole group of remote His50 occupies the fourth labile equatorial position of the previous site. At high Cu(II):αS ratio (>1), His50 leaves the coordination sphere of the first Cu site centered at the N-terminus, because a second weak affinity site centered on His50 is now filled with Cu(II). In this new scheme, the remote His plays the role of a molecular switch and it can be anticipated that the binding of the remote His to the Cu(II) ion can induce different folding of the αS protein, having various aggregation propensity.
ISSN: 0020-1669
DOI: 10.1021/acs.inorgchem.5b00120
Appears in Collections:Publications

Show full item record

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.