Structure of a thermophilic F<inf>1</inf>-ATPase inhibited by an ε-subunit

Deeper insight into the ε-inhibition mechanism

Yasuo Shirakihara, Aya Shiratori, Hiromi Tanikawa, Masayoshi Nakasako, Masasuke Yoshida, Toshiharu Suzuki

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

F<inf>1</inf>-ATPase (F<inf>1</inf>) is the catalytic sector in F<inf>o</inf>F<inf>1</inf>-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 F<inf>1</inf> are inhibited by their own ε-subunit. In the ε-inhibited Escherichia coli F<inf>1</inf> structure, the ε-subunit stabilizes the overall conformation (half-closed, closed, open) of the β-subunits by inserting its C-terminal helix into the α<inf>3</inf>β<inf>3</inf> cavity. The structure of ε-inhibited thermophilic F<inf>1</inf> is similar to that of E. coli F<inf>1</inf>, 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 IF<inf>1</inf> inhibition in mitochondrial F<inf>1</inf>. Database Structural data are available in the Worldwide Protein Data Bank database under the accession number 4XD7 Bacterial F<inf>1</inf>-ATPases including thermophilicF<inf>1</inf> (TF<inf>1</inf>) are inhibited by its ε-subunit. The ε-inhibited TF<inf>1</inf> structure is solved and compared with ε-inhibited E. coli F<inf>1</inf> (EF<inf>1</inf>). TF<inf>1</inf>ε-subunit stabilizes one catalytic subunit's conformation in different form from EF<inf>1</inf>'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.

Original languageEnglish
Pages (from-to)2895-2913
Number of pages19
JournalFEBS Journal
Volume282
Issue number15
DOIs
Publication statusPublished - 2015 Aug 1

Fingerprint

Proton-Translocating ATPases
Conformations
Databases
Escherichia coli
Catalytic Domain
Adenosine Triphosphate
Chloroplasts
Catalysis
Nucleotides
Hooks
Cells
Proteins

Keywords

  • F<inf>1</inf> from thermophilic bacterium
  • F<inf>1</inf>-ATPase
  • second catch
  • ε-inhibition
  • ε-subunit

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Structure of a thermophilic F<inf>1</inf>-ATPase inhibited by an ε-subunit : Deeper insight into the ε-inhibition mechanism. / Shirakihara, Yasuo; Shiratori, Aya; Tanikawa, Hiromi; Nakasako, Masayoshi; Yoshida, Masasuke; Suzuki, Toshiharu.

In: FEBS Journal, Vol. 282, No. 15, 01.08.2015, p. 2895-2913.

Research output: Contribution to journalArticle

Shirakihara, Yasuo ; Shiratori, Aya ; Tanikawa, Hiromi ; Nakasako, Masayoshi ; Yoshida, Masasuke ; Suzuki, Toshiharu. / Structure of a thermophilic F<inf>1</inf>-ATPase inhibited by an ε-subunit : Deeper insight into the ε-inhibition mechanism. In: FEBS Journal. 2015 ; Vol. 282, No. 15. pp. 2895-2913.
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