Nitsche, J, Josts, I, Heidemann, J, Mertens, HD, Maric, S, Moulin, M, Haertlein, M, Busch, S, Forsyth, VT, Svergun, DI, Uetrecht, C and Tidow, H (2018) Structural basis for activation of plasma-membrane Ca(2+)-ATPase by calmodulin. Communications Biology, 1. ISSN 2399-3642

[thumbnail of 20181205_vtf_s42003-018-0203-7.pdf]
20181205_vtf_s42003-018-0203-7.pdf - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview


Plasma-membrane Ca(2+)-ATPases expel Ca(2+) from the cytoplasm and are key regulators of Ca(2+) homeostasis in eukaryotes. They are autoinhibited under low Ca(2+) 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 Ca(2+)-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 Ca(2+) pump in its calmodulin-activated state illustrating a displacement of the regulatory domain from the core enzyme.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Nature Publishing Group at - please refer to any applicable terms of use of the publisher.
Subjects: Q Science > QH Natural history
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 05 Dec 2018 11:54
Last Modified: 01 Mar 2021 14:44

Actions (login required)

View Item
View Item