A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk

Dublin Core

Título

A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk

Tema

PARASITOLOGIA
ECHINOCOCCUS GRANULOSUS
BIBLIOGRAFIA NACIONAL QUIMICA
2009

Abstract

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/ EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (KI *) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection

Autor

González, Silvia
Fló, Martín
Margenat, Mariana
Durán, Rosario
Graña, Martín
Parkinson, John
Maizels, Rick M.
Salinas, Gustavo
Alvarez, Beatriz
Fernández, Cecilia

Fuente

PloS one v. 4, no.9, 2009. -- p. e7009-e7031

Fecha

2009

Formato

PDF

Idioma

Ingles

Tipo

Artículo

Identificador

DOI: 10.1371/journal.pone.0007009
Fecha de agregación
March 20, 2014
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
Etiquetas
,
Citación
González, Silvia, “A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed October 26, 2020, http://riquim.fq.edu.uy/items/show/1325.
Archivos