Deep Insight into the Phosphatomes of Parasitic Protozoa and a Web Resource ProtozPhosDB

<div><p>Phosphorylation dynamically regulates the function of proteins by maintaining a balance between protein kinase and phosphatase activity. A comprehensive understanding of the role phosphatases in cellular signaling is lacking in case of protozoans of medical and veterinary importance worldwide. The drugs used to treat protozoal diseases have many undesired effects and the development of resistance, highlights the need for new effective and safer antiprotozoal agents. In the present study we have analyzed phosphatomes of 15 protozoans of medical significance. We identified ~2000 phosphatases, out of which 21% are uncharacterized proteins. A significant positive correlation between phosphatome and proteome size was observed except for <i>E</i>. <i>histolytica</i>, having highest density of phosphatases irrespective of its proteome size. A difference in the number of phosphatases among different genera shows the variation in the signaling pathways they are involved in. The phosphatome of parasites is dominated by ser/thr phosphatases contrary to the vertebrate host dominated by tyrosine phosphatases. Phosphatases were widely distributed throughout the cell suggesting physiological adaptation of the parasite to regulate its host. 20% to 45% phosphatome of different protozoa consists of ectophosphatases, i.e. crucial for the survival of parasites. A database and a webserver “ProtozPhosDB” can be used to explore the phosphatomes of protozoans of medical significance.</p></div

Bar diagram-representing comparison of PPs in the genomes of parasitic protozoa and human.

<p>The percentage of protein phosphatases genes in the proteome complement is provided against every bar. Species abbreviations used in the diagram are as follows: <i>Gl</i>, <i>Giardia lamblia</i>; <i>Lm</i>, <i>Leishmania major</i>; <i>Tb</i>, <i>Trypanosoma brucei</i>; <i>Tc</i>, <i>Trypanosoma cruzi</i>; <i>Tp, Theileria parva</i>; <i>Bb</i>, <i>Babesia bovis</i>; <i>Tg</i>, <i>Toxoplasma gondii</i>; <i>Cp</i>, <i>Cryptosporidium parvum</i>; <i>Pf</i>, <i>Plasmodium falciparum</i>; <i>Eh</i>, <i>Entamoeba histolytica</i>; <i>Hs</i>, <i>Homo sapiens</i>.</p

Distribution of protozoan parasite phosphatases into families of phosphatases.

<p>Distribution of protozoan parasite phosphatases into families of phosphatases.</p

Analysis of the Protein Phosphotome of <i>Entamoeba histolytica</i> Reveals an Intricate Phosphorylation Network

<div><p>Phosphorylation is the most common mechanism for the propagation of intracellular signals. Protein phosphatases and protein kinases play a dynamic antagonistic role in protein phosphorylation. Protein phosphatases make up a significant fraction of eukaryotic proteome. In this article, we report the identification and analysis of protein phosphatases in the intracellular parasite <i>Entamoeba histolytica</i>. Based on an <i>in silico</i> analysis, we classified 250 non-redundant protein phosphatases in <i>E. histolytica.</i> The phosphotome of <i>E. histolytica</i> is 3.1% of its proteome and 1.3 times of the human phosphotome. In this extensive study, we identified 42 new putative phosphatases (39 hypothetical proteins and 3 pseudophosphatases). The presence of pseudophosphatases may have an important role in virulence of <i>E. histolytica.</i> A comprehensive phosphotome analysis of <i>E. histolytica</i> shows spectacular low similarity to human phosphatases, making them potent candidates for drug target.</p></div

Percentage of phosphatases distributed to different locations of the cell in protozoan parasites.

<p>Percentage of phosphatases distributed to different locations of the cell in protozoan parasites.</p

Venn diagram representing the analyses of conserved and specific functions of phosphatases in protozoan parasite.

<p>Venn diagram representing the analyses of conserved and specific functions of phosphatases in protozoan parasite.</p

Protein phosphatase genes in <i>E. histolytica</i> with varying number of LRR domains.

<p>Protein phosphatase genes in <i>E. histolytica</i> with varying number of LRR domains.</p

Phylogenetic tree representing relationship among EEPs.

<p>Branches with diamond shapes represent hypothetical proteins.</p

Bar diagram-representing comparison of phosphatases in the genomes of parasitic protozoa and human.

<p>Orange bars represents the number of phosphatases reported in previous studies. The percentage of phosphatase genes in the proteome complement is provided against every bar.</p