1. Structural basis for activation of plasma-membrane Ca2+-ATPase by calmodulin
- Author
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Julius Nitsche, Charlotte Uetrecht, V. Trevor Forsyth, Johannes Heidemann, Sebastian Busch, Inokentijs Josts, Dmitri I. Svergun, Michael Haertlein, Selma Maric, Haydyn D. T. Mertens, Martine Moulin, and Henning Tidow
- Subjects
0301 basic medicine ,Medicin och hälsovetenskap ,Calmodulin ,Calcium pump ,ATPase ,Medicine (miscellaneous) ,chemistry.chemical_element ,Calcium ,Q1 ,Medical and Health Sciences ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,ddc:570 ,QD ,lcsh:QH301-705.5 ,chemistry.chemical_classification ,030102 biochemistry & molecular biology ,biology ,QH ,3. Good health ,QR ,030104 developmental biology ,Enzyme ,chemistry ,Membrane protein ,lcsh:Biology (General) ,Cytoplasm ,Biophysics ,biology.protein ,General Agricultural and Biological Sciences ,Homeostasis ,QD415 - Abstract
Communications biology 1(1), 206 (2018). doi:10.1038/s42003-018-0203-7, Plasma-membrane Ca$\mathrm{^{2+}}$-ATPases expel Ca$\mathrm{^{2+}}$ from the cytoplasm and are key regulators of Ca$\mathrm{^{2+}}$ homeostasis in eukaryotes. They are autoinhibited under low Ca$\mathrm{^{2+}}$ 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$\mathrm{^{2+}}$-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$\mathrm{^{2+}}$ pump in its calmodulin-activated state illustrating a displacement of the regulatory domain from the core enzyme., Published by Springer Nature, London
- Published
- 2018