Cryo‐ EM reveals transition states of the Acinetobacter baumannii F 1 ‐ ATPase rotary subunits γ and ε, unveiling novel compound targets
2024; Wiley; Volume: 38; Issue: 20 Linguagem: Inglês
10.1096/fj.202401629r
ISSN1530-6860
AutoresKhoa C. M. Le, Chui Fann Wong, Volker Müller, Gerhard Grüber,
Tópico(s)RNA modifications and cancer
ResumoAbstract Priority 1: critical WHO pathogen Acinetobacter baumannii depends on ATP synthesis and ATP:ADP homeostasis and its bifunctional F 1 F O ‐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 1 ‐αßγε Δ134–139 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.
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