Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii

DOI: 10.1126/sciadv.abl5966

Authors: Julius K. Demmer (Imperial College London) , Ben P. Phillips (Imperial College London) , O. Lisa Uhrig (Imperial College London) , Alain Filloux (Imperial College London) , Luke P. Allsopp (Imperial College London) , Maike Bublitz (University of Oxford) , Thomas Meier (Imperial College London; Private University in the Principality of Liechtenstein)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 8

State: Published (Approved)
Published: February 2022
Diamond Proposal Number(s): 18659

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.

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios III-Titan Krios III at Diamond , Krios IV-Titan Krios IV at Diamond

Other Facilities: London Consortium for electron microscopy (LonCem) at the Crick Institute.

Added On: 22/09/2022 16:54

Documents:
sciadv.abl5966.pdf

Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)