ATP7A and ATP7B are Cu+-transporting ATPases of subclass IB and play a fundamental role in intracellular copper homeostasis. ATP7A/B transfer Cu+ ions across the membrane from delivery to acceptor proteins without establishing a free Cu+ gradient. Transfer of copper across the membrane is coupled to ATP hydrolysis. Current measurements on solid supported membranes (SSM) were performed to investigate the mechanism of copper-related charge transfer across ATP7A and ATP7B. SSM measurements demonstrated that electrogenic copper displacement occurs within ATP7A/B following addition of ATP and formation of the phosphorylated intermediate. Comparison of the time constants for cation displacement in ATP7A/B and sarcoplasmic reticulum Ca2+-ATPase is consistent with the slower phosphoenzyme formation in copper ATPases. Moreover, ATP-dependent copper transfer in ATP7A/B is not affected by varying the pH, suggesting that net proton counter-transport may not occur in copper ATPases. Platinum anticancer drugs activate ATP7A/B and are subjected to ATP-dependent vectorial displacement with a mechanism analogous to that of copper.

Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B / Tadini-Buoninsegni, Francesco*; Smeazzetto, Serena. - In: IUBMB LIFE. - ISSN 1521-6543. - STAMPA. - 69:(2017), pp. 218-225. [10.1002/iub.1603]

Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B

Tadini-Buoninsegni, Francesco
Writing – Original Draft Preparation
;
Smeazzetto, Serena
Membro del Collaboration Group
2017

Abstract

ATP7A and ATP7B are Cu+-transporting ATPases of subclass IB and play a fundamental role in intracellular copper homeostasis. ATP7A/B transfer Cu+ ions across the membrane from delivery to acceptor proteins without establishing a free Cu+ gradient. Transfer of copper across the membrane is coupled to ATP hydrolysis. Current measurements on solid supported membranes (SSM) were performed to investigate the mechanism of copper-related charge transfer across ATP7A and ATP7B. SSM measurements demonstrated that electrogenic copper displacement occurs within ATP7A/B following addition of ATP and formation of the phosphorylated intermediate. Comparison of the time constants for cation displacement in ATP7A/B and sarcoplasmic reticulum Ca2+-ATPase is consistent with the slower phosphoenzyme formation in copper ATPases. Moreover, ATP-dependent copper transfer in ATP7A/B is not affected by varying the pH, suggesting that net proton counter-transport may not occur in copper ATPases. Platinum anticancer drugs activate ATP7A/B and are subjected to ATP-dependent vectorial displacement with a mechanism analogous to that of copper.
2017
69
218
225
Tadini-Buoninsegni, Francesco*; Smeazzetto, Serena
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1114806
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