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

Author(s)

Santos, Viviane Correa ^[1] ; Oliveira, Antonio Edson Rocha ^{[1, 2]} ; Campos, Augusto Cesar Broilo ^[1] ; Reis-Cunha, Joao Luis ^{[3, 4]} ; Bartholomeu, Daniella Castanheira ^[3] ; Teixeira, Santuza Maria Ribeiro ^[1] ; Lima, Ana Paula C. A. ^[5] ; Ferreira, Rafaela Salgado ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Dept Analises Clin & Toxicol, Fac Ciencias Farmaceut, Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Dept Parasitol, Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Dept Med Vet Preventiva, Escola Vet, Belo Horizonte, MG - Brazil

^[5] Univ Fed Rio Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 SEP 14 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/22579-7 - Systems biology applied to transcriptomic analysis of inflammatory diseases
• Grantee: Antonio Edson Rocha Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral