Journal Article

PUBDB-2018-05644

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural basis for activation of plasma-membrane Ca$\mathrm{^{2+}}$-ATPase by calmodulin

Nitsche, J. ; Josts, I. ; Heidemann, J. ; Mertens, H. D.Extern*EMBL* ; Maric, S. ; Moulin, M. ; Haertlein, M. ; Busch, S. ; Forsyth, V. T. ; Svergun, D. I.EMBL* ; Uetrecht, C. ; Tidow, H. (Corresponding author)

2018
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s42003-018-0203-7  doi:10.3204/PUBDB-2018-05644

Abstract: 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.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (POF3-622) (POF3-622)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2018

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Database coverage:
; ; ; DOAJ Seal

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