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

TitleIn situ structure of trypanosomal ATP synthase dimer reveals a unique arrangement of catalytic subunits.
Publication TypeJournal Article
Year of Publication2017
AuthorsMühleip, AW, Dewar, CE, Schnaufer, A, Kühlbrandt, W, Davies, KM
JournalProc Natl Acad Sci U S A
Date Published2017 01 31
KeywordsAdenosine Triphosphate, Amino Acid Sequence, Animals, Catalysis, Catalytic Domain, Consensus Sequence, Dimerization, Euglena gracilis, Mitochondria, Models, Molecular, Protein Conformation, Proton-Translocating ATPases, Protozoan Proteins, Rotation, Sequence Alignment, Sequence Homology, Amino Acid, Trypanosoma brucei brucei

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 F head, in which the catalytic (αβ) 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 α fragments are displaced by ∼20 Å and rotated by ∼30° from their expected positions. In this location, the α 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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.1612386114
PubMed ID28096380
PubMed Central IDPMC5293049
Grant ListG0600129 / / Medical Research Council / United Kingdom
MR/L019701/1 / / Medical Research Council / United Kingdom