8ZI3

Cryo-EM reveals transition states of the Acinetobacter baumannii F1-ATPase rotary subunits gamma and epsilon and novel compound targets - Conformation 4

Summary for 8ZI3

• Entry DOI: 10.2210/pdb8zi3/pdb
• Related: 8ZI0 8ZI1 8ZI2
• EMDB information: 60120
• Descriptor: ATP synthase epsilon chain, ATP synthase subunit alpha, ATP synthase subunit beta, ... (8 entities in total)
• Functional Keywords: atp hydrolysis, f1-atpase, hydrolase
• Biological source: Acinetobacter baumannii AB5075; More
• Total number of polymer chains: 8
• Total formula weight: 365906.58

Authors

Le, K.C.M.,Wong, C.F.,Gruber, G. (deposition date: 2024-05-12, release date: 2024-11-13)

Primary citation

Le, K.C.M.,Wong, C.F.,Muller, V.,Gruber, G.
Cryo-EM reveals transition states of the Acinetobacter baumannii F 1 -ATPase rotary subunits gamma and epsilon , unveiling novel compound targets.
Faseb J., 38:e70131-e70131, 2024

PubMed Abstract: Priority 1: critical WHO pathogen Acinetobacter baumannii depends on ATP synthesis and ATP:ADP homeostasis and its bifunctional FF-ATP synthase. While synthesizing ATP, it regulates ATP cleavage by its inhibitory ε subunit to prevent wasteful ATP consumption. We determined cryo-electron microscopy structures of the ATPase active A. baumannii F-αßγε mutant in four distinct conformational states, revealing four transition states and structural transformation of the ε's C-terminal domain, forming the switch of an ATP hydrolysis off- and an ATP synthesis on-state based. These alterations go in concert with altered motions and interactions in the catalytic- and rotary subunits of this engine. These A. baumannii interacting sites provide novel pathogen-specific targets for inhibitors, with the aim of ATP depletion and/or ATP synthesis and growth inhibition. Furthermore, the presented diversity to other bacterial F-ATP synthases extends the view of structural elements regulating such a catalyst.

PubMed: 39467208
DOI: 10.1096/fj.202401629R

Experimental method

ELECTRON MICROSCOPY (2.89 Å)