Cyclic AMP-dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper-ATPase

Valverde, Rafael H.F.; Morin, Isabelle; Lowe, Jennifer; Mintz, Elisabeth; Cuillel, Martine; Vieyra, Adalberto

doi:10.1016/j.febslet.2008.02.022

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Volume 582, Issue 6 , Pages 891-895, 19 March 2008

Cyclic AMP-dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper-ATPase

Edited by Francesc Posas

This work is dedicated to Leopoldo de Meis on his 70th birthday

Rafael H.F. Valverde
- Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil
Isabelle Morin
- CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux, 17 Rue des Martyrs, Grenoble F-38054, France
- CNRS, UMR 5249, Grenoble F-38054, France
- Université Joseph Fourier, Grenoble F-38000, France
Jennifer Lowe
- Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil
Elisabeth Mintz
- CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux, 17 Rue des Martyrs, Grenoble F-38054, France
- CNRS, UMR 5249, Grenoble F-38054, France
- Université Joseph Fourier, Grenoble F-38000, France
Martine Cuillel
- CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux, 17 Rue des Martyrs, Grenoble F-38054, France
- CNRS, UMR 5249, Grenoble F-38054, France
- Université Joseph Fourier, Grenoble F-38000, France
- Corresponding authors. Addresses: CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux, 17 rue des Martyrs, Grenoble F-38054, France (M. Cuillel), Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil (A. Vieyra). Fax: +33 4 38785487 (M. Cuillel), +55 21 22808193 (A. Vieyra).
Adalberto Vieyra
- Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil
- Corresponding authors. Addresses: CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux, 17 rue des Martyrs, Grenoble F-38054, France (M. Cuillel), Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil (A. Vieyra). Fax: +33 4 38785487 (M. Cuillel), +55 21 22808193 (A. Vieyra).

Received 30 January 2008; accepted 8 February 2008. published online 19 February 2008.

Abstract

The pathogenesis of human Menkes and Wilson diseases depends on alterations in copper transport. Some reports suggest that intracellular traffic of copper might be regulated by kinase-mediated phosphorylation. However, there is no evidence showing the influence of kinase-related processes in coupled ATP hydrolysis/copper transport cycles. Here, we show that cyclic AMP-dependent protein kinase (PKA) regulates Ccc2p, the yeast Cu(I)-ATPase, with PKA-mediated phosphorylation of a conserved serine (Ser²⁵⁸) being crucial for catalysis. Long-range intramolecular communication between Ser²⁵⁸ and Asp⁶²⁷ (at the catalytic site) modulates the key pumping event: the conversion of the high-energy to the low-energy phosphorylated intermediate associated with copper release.

Abbreviations: BCA, bicinchoninic acid, BCS, bathocuproinedisulfonic acid, CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate

Keywords: Ccc2p, Cell signalling, Copper transport, Regulatory phosphorylation, Yeast