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

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 F₁F_o-adenosine 5'-triphosphate (ATP) synthase from <i>A. baumannii</i> 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.