JBIC Journal of Biological Inorganic Chemistry

, Volume 14, Issue 7, pp 995–1000 | Cite as

Importance of dynamical processes in the coordination chemistry and redox conversion of copper amyloid-β complexes

  • Christelle HureauEmail author
  • Véronique Balland
  • Yannick Coppel
  • Pier Lorenzo Solari
  • Emiliano Fonda
  • Peter FallerEmail author


Interaction of Cu ions with the amyloid-β (Aβ) peptide is linked to the development of Alzheimer’s disease; hence, determining the coordination of CuI and CuII ions to Aβ and the pathway of the CuI(Aβ)/CuII(Aβ) redox conversion is of great interest. In the present report, we use the room temperature X-ray absorption near edge structure to show that the binding sites of the CuI and CuII complexes are similar to those previously determined from frozen-solution studies. More precisely, the CuI is coordinated by the imidazole groups of two histidine residues in a linear fashion. However, an NMR study unravels the involvement of all three histidine residues in the CuI binding due to dynamical exchange between several set of ligands. The presence of an equilibrium is also responsible for the complex redox process observed by cyclic voltammetry and evidenced by a concentration-dependent electrochemical response.


Copper Ligand binding Peptide NMR Electrochemistry 




Cyclic voltammogram


Extended X-ray absorption fine structure


Piperazine-1,4-bis(2-ethanesulfonic acid)


Reactive oxygen species


Saturated calomel electrode


X-ray absorption spectroscopy


X-ray absorption near edge structure



This work was supported by a grant from the Agence Nationale de la Recherche, Programme Blanc (NT09-488591, “NEUROMETALS”). The staff of the SAMBA beamline at SOLEIL (SOLEIL Project 20080324) is gratefully acknowledged for help in performing the XAS experiments. We acknowledge Emmanuelle Mothes for technical assistance and Pierre Dorlet for fruitful discussions.

Supplementary material

775_2009_570_MOESM1_ESM.pdf (1.4 mb)
Supplementary material (PDF 1383 kb)


  1. 1.
    Bush AI (2003) Trends Neurosci 26:207–214PubMedCrossRefGoogle Scholar
  2. 2.
    Hureau C, Faller P (2009) Biochimie. doi: 10.1016/j.biochi.2009.1003.1013
  3. 3.
    Faller P, Hureau C (2009) Dalton Trans 1080–1094Google Scholar
  4. 4.
    Shearer J, Szalai VA (2008) J Am Chem Soc 130:17826–17835PubMedCrossRefGoogle Scholar
  5. 5.
    Himes RA, Park GY, Siluvai GS, Blackburn NJ, Karlin KD (2008) Angew Chem Int Ed 47:9084–9087CrossRefGoogle Scholar
  6. 6.
    Syme CD, Nadal RC, Rigby SE, Viles JH (2004) J Biol Chem 279:18169–18177PubMedCrossRefGoogle Scholar
  7. 7.
    Guilloreau L, Damian L, Coppel Y, Mazarguil H, Winterhalter M, Faller P (2006) J Biol Inorg Chem 11:1024–1038PubMedCrossRefGoogle Scholar
  8. 8.
    Karr JW, Szalai VA (2007) J Am Chem Soc 129:3796–3797PubMedCrossRefGoogle Scholar
  9. 9.
    Drew SC, Noble CJ, Masters CL, Hanson GR, Barnham KJ (2009) J Am Chem Soc 131:1195–1207PubMedCrossRefGoogle Scholar
  10. 10.
    Karr JW, Kaupp LJ, Szalai VA (2004) J Am Chem Soc 126:13534–13538PubMedCrossRefGoogle Scholar
  11. 11.
    Streltsov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL, Varghese JN (2008) Biophys J 95:3447–3456PubMedCrossRefGoogle Scholar
  12. 12.
    Minicozzi V, Stellato F, Comai M, Dalla Serra M, Potrich C, Meyer-Klaucke W, Morante S (2008) J Biol Chem 283:10784–10792PubMedCrossRefGoogle Scholar
  13. 13.
    Hou L, Zagorski MG (2006) J Am Chem Soc 128:9260–9261PubMedCrossRefGoogle Scholar
  14. 14.
    Rorabacher DB (2004) Chem Rev 104:651–698PubMedCrossRefGoogle Scholar
  15. 15.
    Jiang D, Man L, Wang J, Zhang Y, Chickenyen S, Wang Y, Zhou F (2007) Biochemistry 46:9270–9282PubMedCrossRefGoogle Scholar
  16. 16.
    Brzyska M, Trzesniewska K, Wieckowska A, Szczepankiewicz A, Elbaum D (2009) Chembiochem 10:1045–1055PubMedCrossRefGoogle Scholar
  17. 17.
    Streltsov VA, Varghese JN (2008) Chem Commun 27:3169–3171Google Scholar
  18. 18.
    Himes RA, Park GY, Barry AN, Blackburn NJ, Karlin KD (2007) J Am Chem Soc 129:5352–5353PubMedCrossRefGoogle Scholar
  19. 19.
    Kau LS, Spira-Solomon DJ, Penner-Hahn JE, Hodgson KO, Solomon EI (1987) J Am Chem Soc 109:6433–6442CrossRefGoogle Scholar
  20. 20.
    Blackburn NJ, Strange RW, Reedijk J, Volbeda A, Farooq A, Karlin KD, Zubieta J (1989) Inorg Chem 28:1349–1357CrossRefGoogle Scholar
  21. 21.
    Guilloreau L, Combalbert S, Sournia-Saquet A, Marzaguil H, Faller P (2007) Chembiochem 8:1317–1325PubMedCrossRefGoogle Scholar
  22. 22.
    Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JDA, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI (1999) J Biol Chem 274:37111–37116PubMedCrossRefGoogle Scholar

Copyright information

© SBIC 2009

Authors and Affiliations

  • Christelle Hureau
    • 1
    • 2
    Email author
  • Véronique Balland
    • 3
  • Yannick Coppel
    • 1
    • 2
  • Pier Lorenzo Solari
    • 4
  • Emiliano Fonda
    • 4
  • Peter Faller
    • 1
    • 2
    Email author
  1. 1.CNRS; LCC (Laboratoire de Chimie de Coordination)ToulouseFrance
  2. 2.Université de Toulouse; UPS, INPT; LCC;ToulouseFrance
  3. 3.Laboratoire d’Electrochimie MoléculaireUnité Mixte de Recherche Université, CNRS No 7591, Université Paris, Diderot, Bâtiment LavoisierParis Cedex 13France
  4. 4.Synchrotron SOLEIL, L’Orme des MerisiersGif-sur-Yvette CedexFrance

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