Identification of cryptic subunits from an apicomplexan ATP synthase
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elife-38097-v1.pdf
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3.09 MB
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Author(s)
Huet, Diego
Rajendran, Esther
van Dooren, Giel G
Lourido, Sebastian
Date Issued
September 2018
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Huet, Diego, Esther Rajendran, Giel G van Dooren, and Sebastian Lourido. “Identification of Cryptic Subunits from an Apicomplexan ATP Synthase.” eLife 7 (September 11, 2018).
Version
Final published version
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. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.7554/eLife.38097
