Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii

Julius K. Demmer; Ben P. Phillips; O. Lisa Uhrig; Alain Filloux; Luke P. Allsopp; Maike Bublitz; Thomas Meier

doi:10.1126/sciadv.abl5966

Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii

Julius K. Demmer, Ben P. Phillips, O. Lisa Uhrig, Alain Filloux, Luke P. Allsopp, Maike Bublitz, Thomas Meier^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

The global spread of multidrug-resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F₁F_o-adenosine 5′-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F₁ subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded F_o complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next-generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.

Original language	English
Article number	eabl5966
Journal	Science advances
Volume	8
Issue number	7
DOIs	https://doi.org/10.1126/sciadv.abl5966
Publication status	Published - Feb 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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title = "Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii",

abstract = "The global spread of multidrug-resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F1Fo-adenosine 5′-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F1 subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded Fo complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next-generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.",

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doi = "10.1126/sciadv.abl5966",

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AU - Phillips, Ben P.

AU - Uhrig, O. Lisa

AU - Filloux, Alain

AU - Allsopp, Luke P.

AU - Bublitz, Maike

AU - Meier, Thomas

N1 - Publisher Copyright: Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

PY - 2022/2

Y1 - 2022/2

N2 - The global spread of multidrug-resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F1Fo-adenosine 5′-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F1 subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded Fo complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next-generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.

AB - The global spread of multidrug-resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F1Fo-adenosine 5′-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F1 subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded Fo complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next-generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.

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Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii

Abstract

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