Enthalpy-entropy compensation at play in human copper ion transfer.
Journal article, 2015

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 C(1)XXC(2) 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.

chemistry

Gel

Amino Acid Motifs

Protein Structure

chemistry

chemistry

Copper

Cation Transport Proteins

Adenosine Triphosphatases

metabolism

Metallochaperones

chemistry

Humans

metabolism

Chromatography

Calorimetry

Tertiary

metabolism

metabolism

Entropy

chemistry

Ions

Author

Moritz S Niemiec

Umeå University

Artur P G Dingeldein

Umeå University

Pernilla Wittung Stafshede

Umeå University

Scientific Reports

2045-2322 (ISSN)

Vol. 5 10518-

Subject Categories

Biological Sciences

Biophysics

DOI

10.1038/srep10518

PubMed

26013029

More information

Latest update

6/12/2019