Lytic water dynamics reveal evolutionarily conserved mechanisms of ATP hydrolysis by TIP49 AAA+ ATPases.

Autor:	Afanasyeva A; Department of Biophysics, Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia; Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute, Gatchina 188300, Russia., Hirtreiter A; Division of Biosciences, Institute for Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK., Schreiber A; Division of Biosciences, Institute for Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK., Grohmann D; Physikalische und Theoretische Chemie - NanoBioSciences, Technische Universität Braunschweig, Braunschweig 38106, Germany., Pobegalov G; Department of Biophysics, Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia., McKay AR; Department of Chemistry, University College London, London WC1H 0AJ, UK., Tsaneva I; Division of Biosciences, Institute for Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK., Petukhov M; Department of Biophysics, Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia; Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute, Gatchina 188300, Russia., Käs E; UMR 5099, CNRS, Toulouse F-31000, France; Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, Toulouse F-31000, France. Electronic address: kas@ibcg.biotoul.fr., Grigoriev M; UMR 5099, CNRS, Toulouse F-31000, France; Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, Toulouse F-31000, France. Electronic address: grigor@biotoul.fr., Werner F; Division of Biosciences, Institute for Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2014 Apr 08; Vol. 22 (4), pp. 549-59. Date of Electronic Publication: 2014 Mar 06.
DOI:	10.1016/j.str.2014.02.002
Abstrakt:	Eukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to their important functions remains largely unknown and difficult to analyze because of the divergent properties of TIP49a and TIP49b proteins and of their homo- and hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed the single ancient TIP49 ortholog found in the archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling and molecular dynamics simulations validated by biochemical assays reveal highly conserved organizational principles and identify key residues for ATP hydrolysis. An unanticipated crosstalk between Walker B and Sensor I motifs impacts the dynamics of water molecules and highlights a critical role of trans-acting aspartates in the lytic water activation step that is essential for the associative mechanism of ATP hydrolysis. (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu