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.

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.

Related Concept Videos

Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...