Copper-Transfer Mechanism from the Human Chaperone Atox1 to a Metal-Binding Domain of Wilson Disease Protein

2010 ◽  
Vol 114 (10) ◽  
pp. 3698-3706 ◽  
Author(s):  
Agustina Rodriguez-Granillo ◽  
Alejandro Crespo ◽  
Dario A. Estrin ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Binding Domain ◽  
Transfer Mechanism ◽  
Wilson Disease Protein ◽  
Metal Binding Domain ◽  
Disease Protein ◽  
Copper Transfer

Copper chaperone Atox1 interacts with the metal-binding domain of Wilson's disease protein in cisplatin detoxification

2013 ◽  
Vol 454 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Nataliya V. Dolgova ◽  
Sergiy Nokhrin ◽  
Corey H. Yu ◽  
Graham N. George ◽  
Oleg Y. Dmitriev
Keyword(s):  
Metal Binding ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Binding Domain ◽  
Binding Motif ◽  
Copper Chaperone ◽  
Copper Binding ◽  
Copper Transporters ◽  
Metal Binding Domain ◽  
Disease Protein

Human copper transporters ATP7B (Wilson's disease protein) and ATP7A (Menkes' disease protein) have been implicated in tumour resistance to cisplatin, a widely used anticancer drug. Cisplatin binds to the copper-binding sites in the N-terminal domain of ATP7B, and this binding may be an essential step of cisplatin detoxification involving copper ATPases. In the present study, we demonstrate that cisplatin and a related platinum drug carboplatin produce the same adduct following reaction with MBD2 [metal-binding domain (repeat) 2], where platinum is bound to the side chains of the cysteine residues in the CxxC copper-binding motif. This suggests the same mechanism for detoxification of both drugs by ATP7B. Platinum can also be transferred to MBD2 from copper chaperone Atox1, which was shown previously to bind cisplatin. Binding of the free cisplatin and reaction with the cisplatin-loaded Atox1 produce the same protein-bound platinum intermediate. Transfer of platinum along the copper-transport pathways in the cell may serve as a mechanism of drug delivery to its target in the cell nucleus, and explain tumour-cell resistance to cisplatin associated with the overexpression of copper transporters ATP7B and ATP7A.

scholarly journals Copper relay path through the N-terminus of Wilson disease protein, ATP7B

Metallomics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1472-1480 ◽  
Author(s):  
Kumaravel Ponnandai Shanmugavel ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Copper Transport ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
N Terminus ◽  
Disease Protein ◽  
Yeast Assay

Using a yeast assay, we identified the roles of ATP7B's six metal-binding domains in internal copper transport and soluble chaperone capacity.

scholarly journals Metal Binding Domains 3 and 4 of the Wilson Disease Protein: Solution Structure and Interaction with the Copper(I) Chaperone HAH1†‡

Biochemistry ◽  
2008 ◽  
Vol 47 (28) ◽  
pp. 7423-7429 ◽  
Author(s):  
Lucia Banci ◽  
Ivano Bertini ◽  
Francesca Cantini ◽  
Amy C. Rosenzweig ◽  
Liliya A. Yatsunyk
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Solution Structure ◽  
Protein Solution ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein
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