Cryo-EM reveals transition states of the Acinetobacter baumannii F 1 -ATPase rotary subunits γ and ε, unveiling novel compound targets.

Autor: Le KCM; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Wong CF; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Müller V; Department of Molecular Microbiology & Bioenergetics, Institute of Molecular Biosciences, Johann Wolfgang Goethe University, Frankfurt, Germany., Grüber G; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Oct; Vol. 38 (20), pp. e70131.
DOI: 10.1096/fj.202401629R
Abstrakt: 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.
(© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
Externí odkaz: