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.
Adenosine Triphosphatases
Amino Acid Motifs
Metallochaperones
Cation Transport Proteins
metabolism
chemistry
Ions
chemistry
chemistry
chemistry
Chromatography
Gel
Tertiary
chemistry
Copper
metabolism
metabolism
Calorimetry
metabolism
Entropy
Protein Structure
Humans
Author
Moritz S Niemiec
Artur P G Dingeldein
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
Scientific Reports
2045-2322 (ISSN)
Vol. 5 10518-Subject Categories (SSIF 2011)
Biological Sciences
Biophysics
DOI
10.1038/srep10518
PubMed
26013029