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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: BIOMOLECULES; v. 11, n. 9 SEP 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 20/13562-0 - Unveiling the role of the immune checkpoint ligand CD200 in the host infection by Leishmania spp.
• Grantee: Mauro Javier Cortez Véliz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/24105-3 - Immunobiology of Leishmania spp.: study of the role of CD200 and biogenesis of parasitophorous vacuole in fagocitic cells infected by Leishmania
• Grantee: Mauro Javier Cortez Véliz
• Support Opportunities: Research Grants - Young Investigators Grants