Structure of ATP synthase from ESKAPE pathogen <i>Acinetobacter baumannii</i>
Julius K. Demmer, Ben P. Phillips, O. Lisa Uhrig, Alain Filloux, Luke P. Allsopp, Maike Bublitz, Thomas Meier
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 F 1 F o –adenosine 5′-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F 1 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.