Dados do Trabalho

Título

In silico prediction of structural and functional aspects of Plasmodium falciparum histidine-rich proteins 2 and 3

Introdução

As the deadliest etiological agent of malaria, Plasmodium falciparum imposes the requirement of rapid diagnostic tests (RDTs) for its timely detection in hard-to-reach endemic areas such as those belonging to the Amazon Basin. Despite being commonly targeted antigens in these RDTs due to a cross reaction, histidine-rich proteins 2 and 3 (HRPs-2/3) still lack a full definition of their respective structures and functions.

Objetivo(s)

This study aimed to predict in silico the residual properties, secondary structure content, post-translational modifications, antigenicity and functional partners of HRPs-2/3.

Material e Métodos

HRPs-2/3 primary structures were derived from the 3D7 reference genome sequence for P. falciparum, converted to the FASTA format and subjected to analysis on the bioinformatics tools PEPSTATS, PREDATOR, PROSCAN, PCPROF and STRING under default settings.

Resultados e Conclusão

HRP-2 showed a lower polar/non-polar amino acid ratio than HRP-3 (1.23 vs. 1.43, respectively). Regarding the secondary structure content, HRP-2 was composed mostly of alpha helices (87.54%) and minorly of random coils (12.46%), while HRP-3 presented a more balanced composition of alpha helices (50.18%) and random coils (48.36%). Moreover, HRPs-2/3 revealed unequal amounts of different patterns of post-translational modifications, namely 2 for HRP-2 (1 N-glycosylation site and 1 N-myristoylation site) and 4 for HRP-3 (3 N-glycosylation sites, 1 protein kinase C phosphorylation site, 1 casein kinase II phosphorylation site and 2 N-myristoylation sites). Besides, potential antigenic sites were distributed along the amino acid sequence of HRP-2 and concentrated in both the N-terminal and C-terminal regions of HRP-3. Among the potential functional partners, HRPs-2/3 were more probable to interact with P. falciparum L-lactate dehydrogenase (PfLDH) and P. falciparum skeleton-binding protein 1 (PfSBP1), respectively. Although HRPs-2/3 are codified by homologous genes from P. falciparum and cross-react in malaria RDTs, they potentially have remarkable differences in their residual properties, secondary structure content, post-translational modifications, antigenicity and functional partners, which may reflect their involvement in distinct roles in the parasite life cycle, potentially influencing the regulation of gene expression and ultimately affecting the precise identification by the available RDTs.

Palavras-chave

Plasmodium falciparum; histidine-rich protein 2; histidine-rich protein 3; protein structure; protein function.