F1-ATPase (F1) is the catalytic sector in FoF1-ATP synthase that is responsible for ATP production in living cells. In catalysis, its three catalytic β-subunits undergo nucleotide occupancy-dependent and concerted open-close conformational changes that are accompanied by rotation of the γ-subunit. Bacterial and chloroplast F1 are inhibited by their own ε-subunit. In the ε-inhibited Escherichia coli F1 structure, the ε-subunit stabilizes the overall conformation (half-closed, closed, open) of the β-subunits by inserting its C-terminal helix into the α3β3 cavity. The structure of ε-inhibited thermophilic F1 is similar to that of E. coli F1, showing a similar conformation of the ε-subunit, but the thermophilic ε-subunit stabilizes another unique overall conformation (open, closed, open) of the β-subunits. The ε-C-terminal helix 2 and hook are conserved between the two structures in interactions with target residues and in their positions. Rest of the ε-C-terminal domains are in quite different conformations and positions, and have different modes of interaction with targets. This region is thought to serve ε-inhibition differently. For inhibition, the ε-subunit contacts the second catches of some of the β- and α-subunits, the N- and C-terminal helices, and some of the Rossmann fold segments. Those contacts, as a whole, lead to positioning of those β- and α- second catches in ε-inhibition-specific positions, and prevent rotation of the γ-subunit. Some of the structural features are observed even in IF1 inhibition in mitochondrial F1. Database Structural data are available in the Worldwide Protein Data Bank database under the accession number 4XD7 Bacterial F1-ATPases including thermophilicF1 (TF1) are inhibited by its ε-subunit. The ε-inhibited TF1 structure is solved and compared with ε-inhibited E. coli F1 (EF1). TF1ε-subunit stabilizes one catalytic subunit's conformation in different form from EF1's. The ε-structures are different except their core regions, thus different inhibition properties. Bacterial ε-inhibition mechanism is now better understood in terms of structure.
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