Structure of ATP synthase from ESKAPE pathogen <i>Acinetobacter baumannii</i>.

Demmer, Julius K; Phillips, Ben P; Uhrig, O Lisa; Filloux, Alain; Allsopp, Luke P; Bublitz, Maike; Meier, Thomas · Sci Adv · 2022

basic_science · Level V

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Abstract

The global spread of multidrug-resistant <i>Acinetobacter baumannii</i> infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F<sub>1</sub>F<sub>o</sub>-adenosine 5'-triphosphate (ATP) synthase from <i>A. baumannii</i> in three distinct conformational states. The nucleotide-converting F<sub>1</sub> subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded F<sub>o</sub> 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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