The novel coccidian micronemal protein MIC11 undergoes proteolytic maturation by sequential cleavage to remove an internal propeptide

• Published in: International journal for parasitology 2004-08, Vol.34 (9), p.1047-1058
• Main Authors: Harper, Jill M., Zhou, Xing W., Pszenny, Viviana, Kafsack, Björn F.C., Carruthers, Vern B.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Apicomplexa; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Calcium - antagonists & inhibitors; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - genetics; Chelating Agents - pharmacology; Disulfide bond; DNA, Complementary - genetics; DNA, Protozoan - genetics; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Electrophoresis, Gel, Two-Dimensional; Female; Fundamental and applied biological sciences. Psychology; Internal propeptide; Life cycle. Host-agent relationship. Pathogenesis; Mass Spectrometry; Mice; Mice, Inbred BALB C; Microneme; Molecular Sequence Data; Proteolytic processing; Protozoa; Protozoan Proteins - analysis; Protozoan Proteins - genetics; Sequence Analysis, DNA; Toxoplasma - chemistry; Toxoplasma - drug effects; Toxoplasma - genetics; Toxoplasma gondii
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2004.05.006

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 α-chain and β-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.