ATP Synthase F_of₁ Structure, Function, and Structure-based Drug Design

Authors

Alexey V. Vlasov, Moscow Institute of Physics and Technology
Stepan D. Osipov, Moscow Institute of Physics and Technology
Nikolay A. Bondarev, Moscow Institute of Physics and Technology
Vladimir N. Uversky, University of South FloridaFollow
Valentin I. Borshchevskiy, Moscow Institute of Physics and Technology
Mikhail F. Yanyushin, Institute of Basic Biological Problems of the Russian Academy of Sciences
Ilya V. Manukhov, Moscow Institute of Physics and Technology
Andrey V. Rogachev, Moscow Institute of Physics and Technology
Anastasiia D. Vlasova, Moscow Institute of Physics and Technology
Nikolay S. Ilyinsky, Moscow Institute of Physics and Technology
Alexandr I. Kuklin, Moscow Institute of Physics and Technology
Norbert A. Dencher, Moscow Institute of Physics and Technology
Valentin I. Gordeliy, Moscow Institute of Physics and Technology

Document Type

Article

Publication Date

2022

Keywords

FOF1 ATP Synthase, Membrane Proteins Intrinsically Disordered Proteins (IDP), Small-molecule Cofactors, Isopronoid Quinones, Structure-based Drug Design

Digital Object Identifier (DOI)

https://doi.org/10.1007/s00018-022-04153-0

Abstract

ATP synthases are unique rotatory molecular machines that supply biochemical reactions with adenosine triphosphate (ATP)—the universal “currency”, which cells use for synthesis of vital molecules and sustaining life. ATP synthases of F-type (FOF1) are found embedded in bacterial cellular membrane, in thylakoid membranes of chloroplasts, and in mitochondrial inner membranes in eukaryotes. The main functions of ATP synthases are control of the ATP synthesis and transmembrane potential. Although the key subunits of the enzyme remain highly conserved, subunit composition and structural organization of ATP synthases and their assemblies are significantly different. In addition, there are hypotheses that the enzyme might be involved in the formation of the mitochondrial permeability transition pore and play a role in regulation of the cell death processes. Dysfunctions of this enzyme lead to numerous severe disorders with high fatality levels. In our review, we focus on FOF1-structure-based approach towards development of new therapies by using FOF1 structural features inherited by the representatives of this enzyme family from different taxonomy groups. We analyzed and systematized the most relevant information about the structural organization of FOF1 to discuss how this approach might help in the development of new therapies targeting ATP synthases and design tools for cellular bioenergetics control.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Cellular and Molecular Life Sciences, v. 79, art. 179

Scholar Commons Citation

Vlasov, Alexey V.; Osipov, Stepan D.; Bondarev, Nikolay A.; Uversky, Vladimir N.; Borshchevskiy, Valentin I.; Yanyushin, Mikhail F.; Manukhov, Ilya V.; Rogachev, Andrey V.; Vlasova, Anastasiia D.; Ilyinsky, Nikolay S.; Kuklin, Alexandr I.; Dencher, Norbert A.; and Gordeliy, Valentin I., "ATP Synthase F_of₁ Structure, Function, and Structure-based Drug Design" (2022). Molecular Medicine Faculty Publications. 998.
https://digitalcommons.usf.edu/mme_facpub/998