Contribution of individual histidines to prion protein copper binding

Paul Davies, Patrick C McHugh, Victoria J Hammond, Frank Marken, David R Brown

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The prion protein is well-established as a copper binding protein. The N-terminus of the protein contains an octameric repeat region with each of the four repeats containing a histidine. The N-terminus has two additional histidines distal to the repeat region that has been commonly known as the fifth site. While binding of copper by the protein has been extensively studied, the contribution of each histidine to copper binding in the full-length protein has not. Here we used a battery of mutants of the recombinant mouse prion protein to assess copper binding with both isothermal titration calorimetry and cyclic voltammetry. The findings indicate that there is extensive cooperativity between different binding sites in the protein. The two highest-affinity binding events occur at the fifth site and at the octameric repeat region. However, the first binding is that to the octameric repeat region. Subsequent binding events after the two initial binding events have lower affinities within the octameric repeat region.

Original languageEnglish
Pages (from-to)10781-91
Number of pages11
JournalBiochemistry
Volume50
Issue number50
DOIs
Publication statusPublished - 20 Dec 2011
Externally publishedYes

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Histidine
Protein Binding
Copper
Calorimetry
Proteins
Titration
Cyclic voltammetry
Binding Sites
Prion Proteins
copper-binding protein
Prions

Cite this

Davies, Paul ; McHugh, Patrick C ; Hammond, Victoria J ; Marken, Frank ; Brown, David R. / Contribution of individual histidines to prion protein copper binding. In: Biochemistry. 2011 ; Vol. 50, No. 50. pp. 10781-91.
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Davies, P, McHugh, PC, Hammond, VJ, Marken, F & Brown, DR 2011, 'Contribution of individual histidines to prion protein copper binding', Biochemistry, vol. 50, no. 50, pp. 10781-91. https://doi.org/10.1021/bi2012349

Contribution of individual histidines to prion protein copper binding. / Davies, Paul; McHugh, Patrick C; Hammond, Victoria J; Marken, Frank; Brown, David R.

In: Biochemistry, Vol. 50, No. 50, 20.12.2011, p. 10781-91.

Research output: Contribution to journalArticle

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AU - McHugh, Patrick C

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