Molecular and biochemical characterization of a cathepsin B-like protease family unique to Trypanosoma congolense
| Autor: | Edith Authié, Théo Baltz, Theresa H.T. Coetzer, Nicolas Biteau, Virginie Coustou, C. Giroud, Carlos Mendoza-Palomares, Alain Boulangé |
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| Přispěvatelé: | Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire biologie moléculaire et immunologie de protozoaires parasites, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2 - Centre National de la Recherche Scientifique (CNRS), Université de Lyon - Université de Lyon - Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Programme forêts naturelles (Cirad-Forêt programme Forêts naturelles), Département Forêt (Cirad-FORET), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), UMR Trypanosomes, Institut de Recherche pour le Développement (IRD)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD) |
| Rok vydání: | 2008 |
| Předmět: |
MESH : Molecular Sequence Data
Trypanosoma congolense [SDV]Life Sciences [q-bio] Cathepsin E MESH: Amino Acid Sequence Cathepsin F L73 - Maladies des animaux Cathepsin A Cathepsin B Cathepsin C MESH: Recombinant Proteins 0302 clinical medicine Cathepsin O Cathepsin H Cathepsin L1 Immunologie MESH: Animals MESH: Phylogeny Phylogeny 0303 health sciences MESH : Amino Acid Sequence MESH : Sequence Alignment Contrôle de maladies MESH : Trypanosoma congolense Cystéine General Medicine Articles MESH: Trypanosoma congolense Recombinant Proteins 3. Good health [SDV] Life Sciences [q-bio] [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology PCR Biochemistry Multigene Family Protéase MESH : Recombinant Proteins 030231 tropical medicine Molecular Sequence Data MESH : Multigene Family MESH: Sequence Alignment MESH : Cathepsins Biology Microbiology 03 medical and health sciences Animals Peptidase Amino Acid Sequence [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology Molecular Biology 030304 developmental biology MESH: Molecular Sequence Data Anticorps MESH : Phylogeny Molecular biology Cathepsins MESH: Cathepsins MESH: Multigene Family MESH : Animals Sequence Alignment |
| Zdroj: | Eukaryotic Cell Eukaryotic Cell, American Society for Microbiology, 2008, 7 (4), pp.684-97. ⟨10.1128/EC.00405-07⟩ Eukaryotic Cell, American Society for Microbiology, 2008, 7 (4), pp.684-97. 〈10.1128/EC.00405-07〉 Eukaryotic Cell, American Society for Microbiology, 2008, 7 (4), pp.684-697 |
| ISSN: | 1535-9786 1535-9778 |
| Popis: | Cysteine proteases have been shown to be essential virulence factors and drug targets in trypanosomatids and an attractive antidisease vaccine candidate forTrypanosoma congolense. Here, we describe an important amplification of genes encoding cathepsin B-like proteases unique toT. congolense. More than 13 different genes were identified, whereas only one or two highly homologous genes have been identified in other trypanosomatids. These proteases grouped into three evolutionary clusters: TcoCBc1 to TcoCBc5 and TcoCBc6, which possess the classical catalytic triad (Cys, His, and Asn), and TcoCBs7 to TcoCBs13, which contains an unusual catalytic site (Ser, Xaa, and Asn). Expression profiles showed that members of the TcoCBc1 to TcoCBc5 and the TcoCBs7 to TcoCBs13 groups are expressed mainly in bloodstream forms and localize in the lysosomal compartment. The expression of recombinant representatives of each group (TcoCB1, TcoCB6, and TcoCB12) as proenzymes showed that TcoCBc1 and TcoCBc6 are able to autocatalyze their maturation 21 and 31 residues, respectively, upstream of the predicted start of the catalytic domain. Both displayed a carboxydipeptidase function, while only TcoCBc1 behaved as an endopeptidase. TcoCBc1 exhibited biochemical differences regarding inhibitor sensitivity compared to that of other cathepsin B-like proteases. Recombinant pro-TcoCBs12 did not automature in vitro, and the pepsin-matured enzyme was inactive in tests with cathepsin B fluorogenic substrates. In vivo inhibition studies using CA074Me (a cell-permeable cathepsin B-specific inhibitor) demonstrated that TcoCB are involved in lysosomal protein degradation essential for survival in bloodstream form. Furthermore, TcoCBc1 elicited an important immune response in experimentally infected cattle. We propose this family of proteins as a potential therapeutic target and as a plausible antigen forT. congolensediagnosis. |
| Databáze: | OpenAIRE |
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