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. 2023 Jul 7;17:1226630. doi: 10.3389/fncel.2023.1226630

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Copyright © 2023 Novorolsky, Kasheke, Hakim, Foldvari, Dorighello, Sekler, Vuligonda, Sanders, Renden, Wilson and Robertson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Representative model of the NCLX showing the regulatory domains and sites. (A) The NCLX regulatory loop is located between the two catalytic α1 and α2 domains. NCLX has a Ψ_m sensing allosteric site as well as a PKA-dependent phosphorylation site Ser258. (B) The Ψ_m provides the driving force for the electrogenic transport of three Na⁺ ions for one Ca²⁺ ion. Phosphorylation of Ser258 by PKA increases NCLX activity. (See section “5.1. Functional architecture of the NCLX” for abbreviations and mechanistic details).