Article
- The EMBO Journal (2006) 25, 2305 - 2314
- doi:10.1038/sj.emboj.7601135
Published online: 18 May 2006
Subject Categories:
Modulatory and catalytic modes of ATP binding by the calcium pump
Anne-Marie Lund Jensen1, Thomas Lykke-Møller Sørensen1,a, Claus Olesen2, Jesper Vuust Møller2 and Poul Nissen1
- Department of Molecular Biology, Aarhus University, Denmark
- Institute of Physiology and Biophysics, Aarhus University, Denmark
Correspondence to:
Poul Nissen, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10c, Aarhus, 8000, Denmark. Tel.: +45 8942 5025; Fax: +45 8612 3178; E-mail: pn@mb.au.dk
Jesper Vuust Møller, Institute of Physiology and Biophysics, Aarhus University, Denmark. Tel.: +45 8942 2938; Fax: +45 8612 9599; E-mail: jvm@biophys.au.uk
aPresent address: Diamond Light Source Ltd, Rutherford Appleton Laboratory, Chilton, UK
Received 21 December 2005; Accepted 19 April 2006
Abstract
We present crystal structures of the calcium-free E2 state of the sarcoplasmic reticulum Ca2+-ATPase, stabilized by the inhibitor thapsigargin and the ATP analog AMPPCP. The structures allow us to describe the ATP binding site in a modulatory mode uncoupled from the Asp351 phosphorylation site. The Glu439 side chain interacts with AMPPCP via an Mg2+ ion in accordance with previous Fe2+-cleavage studies implicating this residue in the ATPase cycle and in magnesium binding. Functional data on Ca2+ mediated activation indicate that the crystallized state represents an initial stage of ATP modulated deprotonation of E2, preceding the binding of Ca2+ ions in the membrane from the cytoplasmic side. We propose a mechanism of Ca2+ activation of phosphorylation leading directly from the compact E2-ATP form to the Ca2E1-ATP state. In addition, a role of Glu439 in ATP modulation of other steps of the functional cycle is suggested.
Keywords:
- Ca2+-ATPase,
- membrane protein crystallography,
- modulatory,
- P-type ATPase,
- transport
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