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Identification of cryptic stator subunits from an apicomplexan ATP synthase

Diego Huet, Esther Rajendran, Giel G. Van Dooren, View ORCID ProfileSebastian Lourido
doi: https://doi.org/10.1101/314385
Diego Huet
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
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Esther Rajendran
2Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
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Giel G. Van Dooren
2Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
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Sebastian Lourido
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
3Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
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  • ORCID record for Sebastian Lourido
  • For correspondence: lourido@wi.mit.edu
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ABSTRACT

The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Hidden Markov modeling suggests that two of them—ICAP2 and ICAP18—share distant homology with mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

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Posted May 11, 2018.
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Identification of cryptic stator subunits from an apicomplexan ATP synthase
Diego Huet, Esther Rajendran, Giel G. Van Dooren, Sebastian Lourido
bioRxiv 314385; doi: https://doi.org/10.1101/314385
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Identification of cryptic stator subunits from an apicomplexan ATP synthase
Diego Huet, Esther Rajendran, Giel G. Van Dooren, Sebastian Lourido
bioRxiv 314385; doi: https://doi.org/10.1101/314385

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