Oligopeptidase B, a missing enzyme in mammals and a potential drug target for trypanosomatid diseases

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

“…TS and iTS Both PI3K/Akt and MAPK/Erk Promotion of invasion and sialylation pattern Butler et al, 2013;Campetella et al, 2020) Tc85 Surface ERK1/2 Host cell attachment and invasion (Magdesian et al, 2007;Mattos et al, 2014) TSSA Surface ERK1/2 Host cell attachment and Ca 2+ signaling (Cańepa et al, 2012a;Caḿara et al, 2017) TcOPB Secreted PLC and Rac1 Produces an unknown structure soluble factor that triggers Ca 2+ mobilization (Caler et al, 1998;Motta et al, 2019) Extracellular (Wainszelbaum et al, 2001;Belaunzarań et al, 2007) All forms Cruzipain Secreted PI3K/Akt and MEK/ERK Ca 2+ signaling (Taketo et al, 1997;San Francisco et al, 2017) gp90 was observed in a poor invasive strain (G) (Ruiz et al, 1998). Although gp90 binds to the host cell, it fails to trigger cytosolic Ca 2+ mobilization (Ruiz et al, 1998).…”

“…Oligopeptidase B (OPB), a serine endopeptidase from the prolyl oligopeptidase family, is conserved in trypanosomatids but not present in any mammalian genome (Motta et al, 2019). OPB has a cytosolic localization and there is not any strong evidence suggesting its secretion by the parasite.…”

“…Surprisingly, even today, with genomes of several T. cruzi strains available, the identity of the precursor it is still unknown. However, the secretion of OPB cannot be ruled out since OPB activity has been found in trypomastigotes supernatants (Fernandes et al, 2005;Motta et al, 2019). Trypanosoma brucei and Trypanosoma evansi OPBs, are released into the extracellular milieu and contribute to pathogenesis by hydrolyzing host circulating factors (Motta et al, 2019).…”

“…However, the secretion of OPB cannot be ruled out since OPB activity has been found in trypomastigotes supernatants (Fernandes et al, 2005;Motta et al, 2019). Trypanosoma brucei and Trypanosoma evansi OPBs, are released into the extracellular milieu and contribute to pathogenesis by hydrolyzing host circulating factors (Motta et al, 2019). In the case of T. cruzi, hydrolyzed peptides would mimics ligands capable of activating GPCR and/or RTK (Motta et al, 2019).…”

Propriedades biológicas da proteína miosina-1 e do receptor dectina-1 na infecção in vitro por Trypanosoma cruzi

“…Tripomastigotas obtidos de cultura de células (TCTs) apresentam outros tipos de moléculas como: gp85é uma glicoproteína de superfície com capacidade de reconhecer fibronectina, citoqueratina e laminina (são componentes da matriz extracelular) e facilitar o processo de invasão (CAMPO et al, 2016); cruzipaína (gp57/51)é uma cisteína protease secretada envolvida na invasão e desenvolvimento celular, importante para a sobrevivência do parasita, além disso é presente em todas as formas evolutivas de T. cruzi (SAN FRANCISCO et al, 2017); oligopeptidase Bé uma serina protease secretada envolvida diretamente na capacidade infectiva de T. cruzi e presente em todas as formas evolutivas (MOTTA et al, 2019); SAP (proteínas ricas em serina, alanina e prolina) -são proteínas secretadas que aderem na superfície celulares, induzindo a entrada de cálcio e promovendo a invasão celular (BAIDA et al, 2006). P21 (proteína 21 de T. cruzi) é uma proteína secretada por T. cruzi e possui um importante papel durante o processo de invasão, todas as suas formas evolutivas expressam essa proteína.…”