In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles
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2021
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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 . 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.