Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B.
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. © 2016 IUBMB Life, 69(4):218-225, 2017.
Department of Chemistry "Ugo Schiff,", University of Florence, Sesto Fiorentino, Italy.
Francesco
0000-0001-5594-2554
F
Tadini-Buoninsegni
Department of Chemistry "Ugo Schiff,", University of Florence, Sesto Fiorentino, Italy.
Serena
S
Smeazzetto
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001692:Biological Transport / Q000187:drug effects; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010984:Platinum / Q000008:administration & dosage / Q000737:chemistry; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D010984:Platinum; D003300:Copper; D000251:Adenosine Triphosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
charge displacement; charge transfer measurements; electrogenic copper movement; mammalian copper ATPases; platinum anticancer drugs; solid supported membrane