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Published July 10, 2013 | public
Journal Article

On Allosteric Modulation of P-Type Cu^+-ATPases

Abstract

P-type ATPases perform active transport of various compounds across biological membranes and are crucial for ion homeostasis and the asymmetric composition of lipid bilayers. Although their functional cycle share principles of phosphoenzyme intermediates, P-type ATPases also show subclass-specific sequence motifs and structural elements that are linked to transport specificity and mechanistic modulation. Here we provide an overview of the Cu^+-transporting ATPases (of subclass P_IB) and compare them to the well-studied sarco(endo)plasmic reticulum Ca^2+-ATPase (of subclass P_IIA). Cu+ ions in the cell are delivered by soluble chaperones to Cu^+-ATPases, which expose a putative "docking platform" at the intracellular interface. Cu^+-ATPases also contain heavy-metal binding domains providing a basis for allosteric control of pump activity. Database analysis of Cu^+ ligating residues questions a two-site model of intramembranous Cu^+ binding, and we suggest an alternative role for the proposed second site in copper translocation and proton exchange. The class-specific features demonstrate that topological diversity in P-type ATPases may tune a general energy coupling scheme to the translocation of compounds with remarkably different properties.

Additional Information

© 2013 Elsevier B.V. Received 11 January 2013; Received in revised form 4 March 2013; Accepted 4 March 2013 Available online 13 March 2013. This work was supported by the Graduate School of Science and Technology of Aarhus University to D.M., O.S. and H.E.A.. G.M. is supported by a Marie Curie International Outgoing Fellowship (European Commission, grant no. 252961); P.N. is supported by the European Research Council through an advanced research project, BIOMEMOS.

Additional details

Created:
August 22, 2023
Modified:
October 24, 2023