Mitochondrial ATP synthase: Crystal structure of the catalytic F 1 unit in a vanadate-induced transition-like state and implications for mechanism

Chen Chen, Ajay K. Saxena, William N. Simcoke, David N. Garboczi, Peter L. Pedersen, Young H. Ko

Research output: Contribution to journalArticle

Abstract

ATP synthesis from ADP, Pi, and Mg2+ takes place in mitochondria on the catalytic F1 unit (α3β 3γδε) of the ATP synthase complex (F 0F1), a remarkable nanomachine that interconverts electrochemical and mechanical energy, producing the high energy terminal bond of ATP. In currently available structural models of F1, the P-loop (amino acid residues 156GGAGVGKT163) contributes to substrate binding at the β subunit catalytic sites. Here, we report the first transition state-like structure of F1 (ADP·V i·Mg·F1) from rat liver that was crystallized with the phosphate (Pi) analog vanadate (VO 43- or Vi). Compared with earlier "ground state" structures, this new F1 structure reveals that the active site region has undergone significant remodeling. P-loop residue alanine 158 is located much closer to Vi than it is to Pi in a previous structural model. No significant movements of P-loop residues of the α subunit were observed at its analogous but noncatalytic sites. Under physiological conditions, such active site remodeling involving the small hydrophobic alanine residue may promote ATP synthesis by lowering the local dielectric constant, thus facilitating the dehydration of ADP and Pi. This new crystallographic study provides strong support for the catalytic mechanism of ATP synthesis deduced from earlier biochemical studies of liver F1 conducted in the presence of Vi (Ko, Y. H., Bianchet, M., Amzel, L. M., and Pedersen, P. L. (1997) J. Biol. Chem. 272, 18875-18881; Ko, Y. H., Hong, S., and Pedersen, P. L. (1999) J. Biol. Chem. 274, 28853-28856).

Original languageEnglish (US)
Pages (from-to)13777-13783
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number19
DOIs
StatePublished - May 12 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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