The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms
Gp82 is a surface glycoprotein expressed in Trypanosoma cruzi metacyclic trypomastigotes, the parasite forms from the insect vector that initiate infection in the mammalian host. Studies with metacyclic forms generated in vitro, as counterparts of insect-
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The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms Cristian Cortez, Tiago J.P. Sobreira, Fernando Y. Maeda, and Nobuko Yoshida
Abstract Gp82 is a surface glycoprotein expressed in Trypanosoma cruzi metacyclic trypomastigotes, the parasite forms from the insect vector that initiate infection in the mammalian host. Studies with metacyclic forms generated in vitro, as counterparts of insect-borne parasites, have shown that gp82 plays an essential role in host cell invasion and in the establishment of infection by the oral route. Among the gp82 properties relevant for infection are the gastric mucin-binding capacity and the ability to induce the target cell signaling cascades that result in actin cytoskeleton disruption and lysosome exocytosis, events that facilitate parasite internalization. The gp82 sequences from genetically divergent T. cruzi strains are highly conserved, displaying >90 % identity. Both the host cell-binding sites, as well as the gastric mucin-binding sequence of gp82, are localized in the C-terminal domain of the molecule. In the gp82 structure model, the main cell-binding site consists of an α-helix, which connects the N-terminal β-propeller domain to the C-terminal β-sandwich domain, where the second cell binding site is nested. The two cell binding sites are fully exposed on gp82 surface. Downstream and close to the α-helix is the gp82 gastric mucin-binding site, which is partially exposed. All available data support the notion that gp82 is structurally suited for metacyclic trypomastigote invasion of host cells and for initiating infection by the oral route.
C. Cortez • F.Y. Maeda • N. Yoshida (*) Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Pedro de Toledo, 669 – 6º andar, 04039-032 São Paulo, SP, Brazil e-mail: [email protected] T.J.P. Sobreira Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, Brazil A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_6, © Springer Science+Business Media Dordrecht 2014
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Abbreviations ACD DAG EIEC GST IP3 MT mTOR PI3K PTK TCT PKC PLC
1
Acute Chagas’ disease Diacylglycerol Enteroinvasive Escherichia coli Glutathione S transferase Inositol 1,4,5-triphosphate Metacyclic trypomastigotes Mammalian target of rapamycin Phosphatidylinositol 3-kinase Protein tyrosine kinase Tissue culture trypomastigotes Protein kinase C Phospholipase C
Introduction
Trypanosoma cruzi metacyclic trypomastigotes (MT) are the developmental forms responsible for the initial parasite-vertebrate host interaction. They are found in the terminal portions of the triatomine insect digestive tract as well as in the anal gland of opossum (Didelphis marsupialis), which is an important reservoir of T. cruzi (Deane et al. 1984). Since the first report on an outbreak of acute Chagas’ disease (ACD) attributed to ingestion of food conta
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