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Enthalpy-entropy compensation at play in human copper ion transfer
Umeå University, Faculty of Science and Technology, Department of Chemistry. (Pernilla Wittung-Stafshede)
Umeå University, Faculty of Science and Technology, Department of Chemistry. (Gerhard Gröbner)
Umeå University, Faculty of Science and Technology, Department of Chemistry. (Pernilla Wittung-Stafshede)
2015 (English)In: Scientific Reports, ISSN 2045-2322, Vol. 5, 10518Article in journal (Refereed) Published
Abstract [en]

Copper (Cu) is an essential trace element but toxic in free form. After cell uptake, Cu is transferred, via direct protein-protein interactions, from the chaperone Atox1 to the Wilson disease protein (WD) for incorporation into Cu-dependent enzymes. Cu binds to a conserved C1XXC2 motif in the chaperone as well as in each of the cytoplasmic metal-binding domains of WD. Here, we dissect mechanism and thermodynamics of Cu transfer from Atox1 to the fourth metal binding domain of WD. Using chromatography and calorimetry together with single Cys-to-Ala variants, we demonstrate that Cu-dependent protein heterocomplexes require the presence of C-1 but not C-2. Comparison of thermodynamic parameters for mutant versus wild type reactions reveals that the wild type reaction involves strong entropy-enthalpy compensation. This property is explained by a dynamic inter-conversion of Cu-Cys coordinations in the wild type ensemble and may provide functional advantage by protecting against Cu mis-ligation and bypassing enthalpic traps.

Place, publisher, year, edition, pages
2015. Vol. 5, 10518
Keyword [en]
copper chaperone, Atox1, Wilson disease protein, metal transport, size exclusion chromatography, thermodynamics, calorimetry
National Category
Biophysics Biochemistry and Molecular Biology Inorganic Chemistry
Research subject
URN: urn:nbn:se:umu:diva-106506DOI: 10.1038/srep10518ISI: 000355537200002PubMedID: 26013029OAI: diva2:841993
Available from: 2015-07-16 Created: 2015-07-14 Last updated: 2015-07-16Bibliographically approved

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Niemiec, Moritz S.Dingeldein, Artur P. G.Wittung-Stafshede, Pernilla
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