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Published on: January 27, 2021
The novel coccidian micronemal protein MIC11 undergoes proteolytic maturation by sequential cleavage to remove an
Jill M Harper1, Xing W Zhou, Viviana Pszenny
1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Abstract:
Host cell invasion is a key step in the life cycle of the intracellular parasite Toxoplasma gondii, the causative agent of toxoplasmosis. Attachment and invasion by this parasite is dependent on secretion of proteins from the micronemes, cigar-shaped organelles found in the apical end of the parasite. Although many of these proteins contain adhesive motifs suggestive of a role in parasite attachment, a growing subset of microneme proteins (MICs) do not possess adhesive sequences implying that they have alternative roles. We have identified a novel 16 kDa microneme protein, TgMIC11, that is conserved among several coccidian parasites. As it traffics through the secretory system, TgMIC11 is modified by two successive proteolytic events to remove an internal propeptide, resulting in the mature protein that consists of an alpha-chain and beta-chain tethered by a single disulfide bond. Dual staining immunofluorescence confirmed that TgMIC11 localises to the apical micronemes and, like other micronemal proteins, it is also secreted in a calcium dependent manner. This is the first microneme protein characterised to date in the phylum Apicomplexa that possesses this unique structure and undergoes maturation by removal of an internal propeptide.
Insights
Researchers identified a novel protein, TgMIC11, crucial for Toxoplasma gondii invasion. This microneme protein undergoes unique processing and secretion, offering new insights into parasite pathogenesis and control strategies.
Area of Science:
- Parasitology
- Cell Biology
- Molecular Biology
Background:
- Host cell invasion is essential for the intracellular parasite Toxoplasma gondii's life cycle.
- Microneme proteins (MICs) are secreted from apical organelles and mediate parasite attachment and invasion.
- Some MICs lack adhesive motifs, suggesting diverse functions beyond adhesion.
Purpose of the Study:
- To identify and characterize novel microneme proteins involved in Toxoplasma gondii invasion.
- To investigate the structure, processing, and localization of the newly identified TgMIC11 protein.
Main Methods:
- Protein identification and characterization.
- Analysis of protein trafficking and modification through the secretory system.
- Dual staining immunofluorescence to confirm protein localization.
- Investigation of secretion mechanism (calcium dependence).
Main Results:
- A novel 16 kDa microneme protein, TgMIC11, conserved in coccidian parasites, was identified.
- TgMIC11 undergoes proteolytic processing to remove an internal propeptide, forming a mature alpha- and beta-chain structure linked by a disulfide bond.
- TgMIC11 localizes to apical micronemes and is secreted in a calcium-dependent manner.
- This represents the first characterized Apicomplexa microneme protein with internal propeptide removal.
Conclusions:
- TgMIC11 is a unique microneme protein with a novel maturation process.
- Its secretion mechanism and apical localization highlight its role in parasite invasion.
- Understanding TgMIC11's function may reveal new therapeutic targets for toxoplasmosis.
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