Authors: Christelle Hureau Christelle Mathé Peter Faller Tony A Mattioli Pierre Dorlet
Publish Date: 2008/05/24
Volume: 13, Issue: 7, Pages: 1055-
Abstract
The GGGTHSQW sequence in the amyloidogenic part of the prion protein is a potential binding site for CuII We have previously studied the binding of copper to the shorter GGGTH peptide and showed that it is highly pH dependent Hureau et al in J Biol Inorg Chem 11735–744 2006 Two predominant complexes could be characterized at pH 67 and 90 with equatorial binding modes of 3N1O and 4N for the metal ion respectively In this work we have further investigated the coordination of CuII to the GGGTH peptide as well as the longer GGGTHSQW peptide in order to identify the oxygen donor ligand at neutral pH and to study the proximity and redox activity of the tryptophan residue of the latter The results for both peptides show that at pH 67 CuII is coordinated by a carbonyl peptide backbone At higher pH values the carbonyl ligand dissociates and the coordination changes to a 4N binding mode inducing a structural rearrangement that brings the GGGTHSQW peptide’s tryptophan residue into the vicinity of the copper ion thus affecting their respective redox propertiesThis work was supported by a grant from the Agence Nationale de la Recherche Programme Jeunes Chercheuses Jeunes Chercheurs ANR05JCJC0010 ‘NEUROARPE’ to PD including a postdoctoral fellowship to CM We thank Guillaume Blain for technical assistance and maintenance of the Elexys EPR/ENDOR spectrometer Emmanuelle Mothes and Luc Guilloreau for fluorescence measurements Jérôme Santolini for assistance with the ATRFTIR measurements Alain Boussac for the use of the pulsedEPR spectrometer and Elodie AnxolabéhèreMallart for discussions
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