title: Impact of cofactor on stability of bacterial (CopZ) and human (Atox1) copper chaperones.
abstract: Here, we present the first characterization of in vitro unfolding and thermodynamic stability of two copper chaperone proteins: Bacillus subtilis CopZ and Homo sapiens Atox1. We find that the unfolding reactions for apo- and Cu(I)-forms of CopZ and Atox1, induced by the chemical denaturant, guanidine hydrochloride (GuHCl), and by thermal perturbation are reversible two-state reactions. For both proteins, the unfolding midpoints shift to higher GuHCl concentrations and the thermodynamic stability is increased in the presence of Cu(I). Despite the same overall fold, apo-CopZ exhibits much lower thermal stability than apo-Atox1. Although the thermal stability of both proteins is increased in the presence of copper, the stabilizing effect is largest for the less stable variant. Divergent energetic properties of the apo- and holo-forms may be linked to conformational changes that facilitate copper transfer to the target.
authors: Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, Houston, TX 77251, USA.
authors: Faiza
authors: F
authors: Hussain
authors: Pernilla
authors: P
authors: Wittung-Stafshede
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001412:Bacillus subtilis / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D000079922:Copper Transport Proteins; D006801:Humans; D056511:Metallochaperones; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011489:Protein Denaturation / Q000502:physiology; D017510:Protein Folding; D013816:Thermodynamics
chemical_list: C474500:ATOX1 protein, human; D001059:Apoproteins; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D008667:Metalloproteins; D018832:Molecular Chaperones; D003300:Copper