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.

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

Författare

Moritz S Niemiec

Artur P G Dingeldein

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Scientific Reports

2045-2322 (ISSN)

Vol. 5 10518-

Ämneskategorier

Biologiska vetenskaper

Biofysik

DOI

10.1038/srep10518

PubMed

26013029