Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/138820
Title: The NMR solution structure of Mycobacterium tuberculosis F-ATP synthase subunit ε provides new insight into energy coupling inside the rotary engine
Authors: Joon, Shin
Ragunathan, Priya
Sundararaman, Lavanya
Nartey, Wilson
Kundu, Subhashri
Manimekalai, Malathy Sony Subramanian
Bogdanović, Nebojša
Dick, Thomas
Grüber, Gerhard
Keywords: Science::Biological sciences::Biophysics
Science::Biological sciences::Biochemistry
Issue Date: 2018
Source: Joon, S., Ragunathan, P., Sundararaman, L., Nartey, W., Kundu, S., Manimekalai, M. S. S., . . . Grüber, G. (2018). The NMR solution structure of Mycobacterium tuberculosis F‐ATP synthase subunit ε provides new insight into energy coupling inside the rotary engine. The FEBS Journal, 285(6), 1111-1128. doi:10.1111/febs.14392
Journal: FEBS Journal
Abstract: Mycobacterium tuberculosis (Mt) F1F0 ATP synthase (α3:β3:γ:δ:ε:a:b:b′:c9) is essential for the viability of growing and nongrowing persister cells of the pathogen. Here, we present the first NMR solution structure of Mtε, revealing an N‐terminal β‐barrel domain (NTD) and a C‐terminal domain (CTD) composed of a helix‐loop‐helix with helix 1 and ‐2 being shorter compared to their counterparts in other bacteria. The C‐terminal amino acids are oriented toward the NTD, forming a domain‐domain interface between the NTD and CTD. The Mtε structure provides a novel mechanistic model of coupling c‐ring‐ and ε rotation via a patch of hydrophobic residues in the NTD and residues of the CTD to the bottom of the catalytic α3β3‐headpiece. To test our model, genome site‐directed mutagenesis was employed to introduce amino acid changes in these two parts of the epsilon subunit. Inverted vesicle assays show that these mutations caused an increase in ATP hydrolysis activity and a reduction in ATP synthesis. The structural and enzymatic data are discussed in light of the transition mechanism of a compact and extended state of Mtε, which provides the inhibitory effects of this coupling subunit inside the rotary engine. Finally, the employment of these data with molecular docking shed light into the second binding site of the drug Bedaquiline.
URI: https://hdl.handle.net/10356/138820
ISSN: 1742-464X
DOI: 10.1111/febs.14392
Rights: © 2018 Federation of European Biochemical Societies. All rights reserved. This is the accepted version of the following article: Joon, S., Ragunathan, P., Sundararaman, L., Nartey, W., Kundu, S., Manimekalai, M. S. S., . . . Grüber, G. (2018). The NMR solution structure of Mycobacterium tuberculosis F‐ATP synthase subunit ε provides new insight into energy coupling inside the rotary engine. The FEBS Journal, 285(6), 1111-1128. doi:10.1111/febs.14392, which has been published in final form at https://doi.org/10.1111/febs.14392
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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