Enthalpy-entropy compensation at play in human copper ion transfer.
Artikel i vetenskaplig tidskrift, 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
Författare
Moritz S Niemiec
Umeå universitet
Artur P G Dingeldein
Umeå universitet
Pernilla Wittung Stafshede
Umeå universitet
Scientific Reports
2045-2322 (ISSN) 20452322 (eISSN)
Vol. 5 10518-Ämneskategorier
Biologiska vetenskaper
Biofysik
DOI
10.1038/srep10518
PubMed
26013029