Cryo-EM structure of the Mycobacterium abscessus F1-ATPase

The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis inhibitors brought the oxidative phosphorylation pathway with its final product ATP, formed by the essential F1FO-ATP synthase (su...

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Main Authors: Wong, Chui Fann, Leow, Chen Yen, Grüber, Gerhard
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169214
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1692142023-07-10T15:31:50Z Cryo-EM structure of the Mycobacterium abscessus F1-ATPase Wong, Chui Fann Leow, Chen Yen Grüber, Gerhard School of Biological Sciences Science::Biological sciences::Biochemistry Science::Biological sciences::Biophysics ATP Synthase Bioenergetics Electron Microscopy Infectious Diseases Mycobacterium Non-Tuberculous Mycobacteria The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis inhibitors brought the oxidative phosphorylation pathway with its final product ATP, formed by the essential F1FO-ATP synthase (subunits α3:β3:γ:δ:ε:a:b:b':c9), into focus as an attractive inhibitor target against Mab. Because of the pharmacological attractiveness of this enzyme, we generated and purified a recombinant and enzymatically active Mab F1-ATPase complex, including subunits α3:β3:γ:δ:ε (MabF1-αβγδε) to achieve mechanistic, regulatory, and structural insights. The high purity of the complex enabled the first cryo-electron microscopy structure determination of the Mab F1-ATPase complex to 7.3 Å resolution. The enzyme showed low ATP hydrolysis activity, which was stimulated by trypsin treatment. No effect was observed in the presence of the detergent lauryldimethylamine oxide. National Research Foundation (NRF) Submitted/Accepted version This research was supported by the National Research Foundation (NRF) Singapore, NRF Competitive Research Programme (CRP), Grant Award Number NRF-CRP27- 2021-0002. 2023-07-10T02:19:52Z 2023-07-10T02:19:52Z 2023 Journal Article Wong, C. F., Leow, C. Y. & Grüber, G. (2023). Cryo-EM structure of the Mycobacterium abscessus F1-ATPase. Biochemical and Biophysical Research Communications, 671, 140-145. https://dx.doi.org/10.1016/j.bbrc.2023.05.095 0006-291X https://hdl.handle.net/10356/169214 10.1016/j.bbrc.2023.05.095 671 140 145 en NRF-CRP27-2021-0002 Biochemical and Biophysical Research Communications © 2023 Elsevier Inc. All rights reserved. This paper was published in Biochemical and Biophysical Research Communications and is made available with permission of Elsevier Inc. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Biochemistry
Science::Biological sciences::Biophysics
ATP Synthase
Bioenergetics
Electron Microscopy
Infectious Diseases
Mycobacterium
Non-Tuberculous Mycobacteria
spellingShingle Science::Biological sciences::Biochemistry
Science::Biological sciences::Biophysics
ATP Synthase
Bioenergetics
Electron Microscopy
Infectious Diseases
Mycobacterium
Non-Tuberculous Mycobacteria
Wong, Chui Fann
Leow, Chen Yen
Grüber, Gerhard
Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
description The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis inhibitors brought the oxidative phosphorylation pathway with its final product ATP, formed by the essential F1FO-ATP synthase (subunits α3:β3:γ:δ:ε:a:b:b':c9), into focus as an attractive inhibitor target against Mab. Because of the pharmacological attractiveness of this enzyme, we generated and purified a recombinant and enzymatically active Mab F1-ATPase complex, including subunits α3:β3:γ:δ:ε (MabF1-αβγδε) to achieve mechanistic, regulatory, and structural insights. The high purity of the complex enabled the first cryo-electron microscopy structure determination of the Mab F1-ATPase complex to 7.3 Å resolution. The enzyme showed low ATP hydrolysis activity, which was stimulated by trypsin treatment. No effect was observed in the presence of the detergent lauryldimethylamine oxide.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Wong, Chui Fann
Leow, Chen Yen
Grüber, Gerhard
format Article
author Wong, Chui Fann
Leow, Chen Yen
Grüber, Gerhard
author_sort Wong, Chui Fann
title Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
title_short Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
title_full Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
title_fullStr Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
title_full_unstemmed Cryo-EM structure of the Mycobacterium abscessus F1-ATPase
title_sort cryo-em structure of the mycobacterium abscessus f1-atpase
publishDate 2023
url https://hdl.handle.net/10356/169214
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