title: Structure of a thermophilic F1-ATPase inhibited by an ε-subunit: deeper insight into the ε-inhibition mechanism.
abstract: F1-ATPase (F1) is the catalytic sector in F(o)F1-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.
authors.affiliation: National Institute of Genetics, Mishima, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shirakihara
authors.affiliation: National Institute of Genetics, Mishima, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shiratori
authors.affiliation: National Institute of Genetics, Mishima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tanikawa
authors.affiliation: The Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakasako
authors.affiliation: The Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama, Japan.|ERATO, Japan Science and Technology Corporation (JST), Yokohama, Japan.
authors.forename: Masasuke
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: The Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama, Japan.|ERATO, Japan Science and Technology Corporation (JST), Yokohama, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D011487:Protein Conformation; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006180:Proton-Translocating ATPases
keywords: F1 from thermophilic bacterium; F1-ATPase; second catch; ε-inhibition; ε-subunit