In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

Autor(es)

Orrego, Patricio R. ^[1] ; Serrano-Rodriguez, Mayela ^[2] ; Cortez, Mauro ^[3] ; Araya, Jorge E. ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Antofagasta, Fac Ciencias Salud, Dept Biomed, Antofagasta 1270300 - Chile

^[2] Univ Antofagasta, Fac Ciencias Salud, Dept Tecnol Med, Antofagasta 1270300 - Chile

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508000 Sao Paulo - Brazil

^[4] Univ Antofagasta, Ctr Biotechnol & Bioengn, CeBIB, Antofagasta 1270300 - Chile

• Tipo de documento: Artigo Científico
• Fonte: BIOMOLECULES; v. 11, n. 9 SEP 2021.
• Citações Web of Science: 0

Resumo

Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca2+-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1\_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNA alpha. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease. (AU)

• Processo FAPESP: 20/13562-0 - Desvendando o papel do imune checkpoint ligante CD200 na infecção do hospedeiro por Leishmania spp.
• Beneficiário: Mauro Javier Cortez Véliz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/24105-3 - Imunobiologia de Leishmania spp.: estudo do papel de CD200 e biogênese do vacúolo parasitóforo em células fagocíticas infectadas por Leishmania
• Beneficiário: Mauro Javier Cortez Véliz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores