Cryo-EM structure of the Mycobacterium abscessus F1-ATPase

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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Bibliographic Details
Main Authors: Wong, Chui Fann, Leow, Chen Yen, Grüber, Gerhard
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
Subjects:
Science::Biological sciences::Biochemistry
Science::Biological sciences::Biophysics
ATP Synthase
Bioenergetics
Electron Microscopy
Infectious Diseases
Mycobacterium
Non-Tuberculous Mycobacteria
Online Access:https://hdl.handle.net/10356/169214
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.

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