The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites

Abstract Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. He...

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Autores principales:	Viviane Corrêa Santos, Antonio Edson Rocha Oliveira, Augusto César Broilo Campos, João Luís Reis-Cunha, Daniella Castanheira Bartholomeu, Santuza Maria Ribeiro Teixeira, Ana Paula C. A. Lima, Rafaela Salgado Ferreira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04782922325f4c48a209e0ed361ee524
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spelling	oai:doaj.org-article:04782922325f4c48a209e0ed361ee5242021-12-02T18:02:31ZThe gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites10.1038/s41598-021-97490-22045-2322https://doaj.org/article/04782922325f4c48a209e0ed361ee5242021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97490-2https://doaj.org/toc/2045-2322Abstract Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.Viviane Corrêa SantosAntonio Edson Rocha OliveiraAugusto César Broilo CamposJoão Luís Reis-CunhaDaniella Castanheira BartholomeuSantuza Maria Ribeiro TeixeiraAna Paula C. A. LimaRafaela Salgado FerreiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Viviane Corrêa Santos Antonio Edson Rocha Oliveira Augusto César Broilo Campos João Luís Reis-Cunha Daniella Castanheira Bartholomeu Santuza Maria Ribeiro Teixeira Ana Paula C. A. Lima Rafaela Salgado Ferreira The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
description	Abstract Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.
format	article
author	Viviane Corrêa Santos Antonio Edson Rocha Oliveira Augusto César Broilo Campos João Luís Reis-Cunha Daniella Castanheira Bartholomeu Santuza Maria Ribeiro Teixeira Ana Paula C. A. Lima Rafaela Salgado Ferreira
author_facet	Viviane Corrêa Santos Antonio Edson Rocha Oliveira Augusto César Broilo Campos João Luís Reis-Cunha Daniella Castanheira Bartholomeu Santuza Maria Ribeiro Teixeira Ana Paula C. A. Lima Rafaela Salgado Ferreira
author_sort	Viviane Corrêa Santos
title	The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
title_short	The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
title_full	The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
title_fullStr	The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
title_full_unstemmed	The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
title_sort	gene repertoire of the main cysteine protease of trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04782922325f4c48a209e0ed361ee524
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The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites

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