Giardia fibrillarin: a bioinformatics exploration of sequence and structure

Abstract

Abstract Purpose Fibrillin stands out as an S-adenosyl-L-methionine (SAM)-dependent nucleolar methyltransferase, marked by significant evolutionary conservation in both sequence and function. It is actively involved in numerous cellular processes, particularly in the early stages of pre-ribosomal RNA processing. Despite the identification of a fibrillarin orthologue in Giardia, an intestinal protozoan parasite that annually causes a considerable number of infections worldwide, its study has been limited. Consequently, the specific structural features and functions of this protein in the parasite remain unknown. In this study, bioinformatics methods were employed to scrutinize the sequence and structure of Giardia fibrillarin in order to obtain information that could facilitate future experimental and targeting studies. Taking advantage of the protein sequence of Giardia fibrillarin, multiple bioinformatics tools were employed to estimate its domains, nuclear and nucleolar localization signals (NLS and NoLS), post-translational modifications, phylogeny and three-dimensional structure. Giardia fibrillarin demonstrates significant conservation, showing closer relationships with archaeal and parasitic amoeba orthologs. It retains the SAM-dependent methyltransferase domain, a glycine- and arginine-rich domain, as well as the NLS and NoLS. While the core region remains structurally highly conserved, the N-terminal region shows significant divergence. Inhibition is feasible using competing SAM inhibitors. Further research is needed on Giardia fibrillarin, given its potential as a promising therapeutic target for tackling giardiasis. This is especially important in cases of strains resistant to current drugs, an increasingly common challenge.