N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Myristoylation often primes for subsequent palmitoylation and stable membrane attachment, however, growing evidence suggests additional regulatory roles for myristoylation on proteins. Here we describe the myristoylated proteome of Toxoplasma gondii using chemoproteomic methods and show that a small-molecule NMT inhibitor developed against related Plasmodium spp. is also functional in Toxoplasma. We identify myristoylation on a transmembrane protein, the microneme protein 7 (MIC7), which enters the secretory pathway in an unconventional fashion with the myristoylated N-terminus facing the lumen of the micronemes. MIC7 and its myristoylation play a crucial role in the initial steps of invasion, likely during the interaction with and penetration of the host cell. Myristoylation of secreted eukaryotic proteins represents a substantial expansion of the functional repertoire of this co-translational modification.
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 5, 6 and 7. Source data for mass spectrometry proteomics results can be found in Supplementary files 1-4. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2019) partner repository with the dataset identifier PXD019677.
Global profiling of myristoylation in Toxoplasma gondii.ProteomeXchange, PXD019677.
Differential protein phosphorylation during stage conversion in Toxoplasma gondiiProteomeXchange, PXD019729.
- Malgorzata Broncel
- Caia Dominicus
- Stephanie D Nofal
- Alex Hunt
- Bethan Alexandra Wallbank
- Joanna Claire Young
- Moritz Treeck
- Malgorzata Broncel
- Caia Dominicus
- Moritz Treeck
- Stephen Matthews
- Edward J Bartlett
- Edward W Tate
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Dominique Soldati-Favre, University of Geneva, Switzerland
© 2020, Broncel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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