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Lytic Water Dynamics Reveal Evolutionarily Conserved Mechanisms of ATP Hydrolysis by TIP49 AAA+ ATPases

Afanasyeva, A; Hirtreiter, A; Schreiber, A; Grohmann, D; Pobegalov, G; McKay, AR; Tsaneva, I; ... Werner, F; + view all (2014) Lytic Water Dynamics Reveal Evolutionarily Conserved Mechanisms of ATP Hydrolysis by TIP49 AAA+ ATPases. Structure , 22 (4) pp. 549-559. 10.1016/j.str.2014.02.002. Green open access

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Abstract

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). Allatom 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.

Type: Article
Title: Lytic Water Dynamics Reveal Evolutionarily Conserved Mechanisms of ATP Hydrolysis by TIP49 AAA+ ATPases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.str.2014.02.002
Publisher version: http://doi.org/10.1016/j.str.2014.02.002
Language: English
Additional information: © 2014 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, Cell Biology, BIOCHEMISTRY & MOLECULAR BIOLOGY, BIOPHYSICS, CELL BIOLOGY, CHROMATIN-REMODELING COMPLEX, HEPATOCELLULAR-CARCINOMA, MASS-SPECTROMETRY, PLUS PROTEINS, DNA-BINDING, C-MYC, REPTIN, PONTIN, TRANSCRIPTION, GROWTH
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1423736
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