In situ structure of trypanosomal ATP synthase dimer reveals a unique arrangement of catalytic subunits

Alexander W Muhleip, Caroline Dewar, Achim Schnaufer, Werner Kühlbrandt, Karen M Davies

Research output: Contribution to journalArticlepeer-review

Abstract

We used electron cryotomography and subtomogram averaging to determine the in situ structures of mitochondrial ATP synthase dimers from two organisms belonging to the phylum euglenozoa: Trypanosoma brucei, a lethal human parasite, and Euglena gracilis, a photosynthetic protist. At a resolution of 32.5 Å and 27.5 Å, respectively, the two structures clearly exhibit a noncanonical F1 head, in which the catalytic (αβ)3 assembly forms a triangular pyramid rather than the pseudo-sixfold ring arrangement typical of all other ATP synthases investigated so far. Fitting of known X-ray structures reveals that this unusual geometry results from a phylum-specific cleavage of the α subunit, in which the C-terminal αC fragments are displaced by ∼20 Å and rotated by ∼30° from their expected positions. In this location, the αC fragment is unable to form the conserved catalytic interface that was thought to be essential for ATP synthesis, and cannot convert γ-subunit rotation into the conformational changes implicit in rotary catalysis. The new arrangement of catalytic subunits suggests that the mechanism of ATP generation by rotary ATPases is less strictly conserved than has been generally assumed. The ATP synthases of these organisms present a unique model system for discerning the individual contributions of the α and β subunits to the fundamental process of ATP synthesis.
Original languageEnglish
Pages (from-to)992-997
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume114
Issue number5
Early online date17 Jan 2017
DOIs
Publication statusPublished - 31 Jan 2017

Keywords

  • mitochondrial ATP synthase
  • electron cryo-tomography
  • subtomogram averaging
  • trypanosome
  • rotary catalysis

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