2017 - Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B
SURFE²R ONE (a predecessor model of SURFE²R N1) publication in IUBMB Life (2017)
Tadini-Buoninsegni F., Smeazzetto S.
IUBMB Life (201z) 69(4):218-225
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.