The Toxoplasma gondii protein MIC3 requires pro-peptide cleavage and dimerization to functionas adhesin

AUTOR(ES)

Cérède, Odile

FONTE

Oxford University Press

RESUMO

Attachment and invasion of host cells by apicomplexan parasites involve the exocytosis of the micronemal proteins (MICs). Most MICs are adhesins, which show homology with adhesive domains from higher eukaryote proteins and undergo proteolytic processing of unknown biological significance during their transport to micronemes. In Toxoplasma gondii, the micronemal homodimeric protein MIC3 is a potent adhesin that displays features shared by most Apicomplexa MICs. We have developed an original MIC3-binding assay by transfection of mammalian cells with complete or truncated MIC3 gene sequences and demonstrated that the receptor binding site of MIC3 is located in the N-terminal chitin-binding-like domain, which remains poorly accessible until the adjacent pro-peptide has been cleaved, and that binding requires dimerization. We have localized the dimerization domain in the C-terminal end of the protein and shown that it is able to convert MIC8, a monomeric micronemal protein sharing the MIC3 lectin-like domain, into a dimer able to interact with host cell receptors. These findings shed new light on molecular mechanisms that control functional maturation of MICs.

Documentos Relacionados

• The MIC3 Gene of Toxoplasma gondii Is a Novel Potent Vaccine Candidate against Toxoplasmosis
• Maize ribosome-inactivating protein (b-32). Homologs in related species, effects on maize ribosomes, and modulation of activity by pro-peptide deletions.
• Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii
• Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2–M2AP adhesive protein complex
• CR3-dependent resistance to acute Toxoplasma gondii infection in mice.