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Structure of the ATP synthase catalytic complex (F1) from Escherichia coli in an autoinhibited conformation

Nature Structural & Molecular Biology volume 18, pages 701707 (2011) | Download Citation

Abstract

ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F1) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit ɛ adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts that are incompatible with functional rotation. As a result, the three catalytic subunits are stabilized in a set of conformations and rotational positions distinct from previous F1 structures.

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Acknowledgements

We dedicate this work to the memory of Vladimir Bulygin, Ph.D. (1964–2009), who was instrumental in early stages of the project. We thank M. Hutcheon for skillful protein purification. Financial support was provided by the US National Institutes of Health (R01GM083088). We thank the staff at NSLS beamlines X6A, X25 (Brookhaven National Laboratory, Upton, New York, USA) and at macCHESS (Cornell University, Ithaca, New York, USA) for beam time and assistance in data collection.

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Affiliations

  1. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

    • Gino Cingolani
  2. Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York, USA.

    • Thomas M Duncan

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Contributions

T.M.D. developed a purification protocol to obtain homogeneous EF1-δ. T.M.D. and G.C. crystallized EF1-δ. G.C. collected X-ray data and determined the crystal structure. T.M.D. wrote the manuscript with the help of G.C.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Gino Cingolani or Thomas M Duncan.

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https://doi.org/10.1038/nsmb.2058

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