Nitsche, J, Josts, I, Heidemann, J, Mertens, HD, Maric, S, Moulin, M, Haertlein, M, Busch, S, Forsyth, VT ORCID: https://orcid.org/0000-0003-0380-3477, Svergun, DI, Uetrecht, C and Tidow, H (2018) Structural basis for activation of plasma-membrane Ca2+-ATPase by calmodulin. Communications Biology, 1 (1). 206 - ?.

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Abstract

Plasma-membrane Ca2+-ATPases expel Ca2+ from the cytoplasm and are key regulators of Ca2+ homeostasis in eukaryotes. They are autoinhibited under low Ca2+ concentrations. Calmodulin (CaM)-binding to a unique regulatory domain releases the autoinhibition and activates the pump. However, the structural basis for this activation, including the overall structure of this calcium pump and its complex with calmodulin, is unknown. We previously determined the high-resolution structure of calmodulin in complex with the regulatory domain of the plasma-membrane Ca2+-ATPase ACA8 and revealed a bimodular mechanism of calcium control in eukaryotes. Here we show that activation of ACA8 by CaM involves large conformational changes. Combining advanced modeling of neutron scattering data acquired from stealth nanodiscs and native mass spectrometry with detailed dissection of binding constants, we present a structural model for the full-length ACA8 Ca2+ pump in its calmodulin-activated state illustrating a displacement of the regulatory domain from the core enzyme.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QD Chemistry > QD415 Biochemistry
Q Science > QR Microbiology
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 19 Oct 2020 08:37
Last Modified: 19 Oct 2020 08:37
URI: https://eprints.keele.ac.uk/id/eprint/8698

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