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In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum.

ABSTRACT: The Plasmodium falciparum variant surface antigen PfEMP1 expressed on the surface of infected erythrocytes is thought to play a major role in the pathology of severe malaria. As the sequence pool of the var genes encoding PfEMP1 expands there are opportunities, despite the high degree of sequence diversity demonstrated by this gene family, to reconstruct full-length var genes from small sequence tags generated from patient isolates. To test whether this is possible we have used a set of recently laboratory adapted ICAM-1-binding parasite isolates to generate sequence tags and, from these, to identify the full-length PfEMP1 being expressed by them. In a subset of the strains available we were able to produce validated, full-length var gene sequences and use these to conduct biophysical analyses of the ICAM-1 binding regions.

SUBMITTER: Carrington E

PROVIDER: S-EPMC5818487 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum.

Carrington Eilidh E Otto Thomas D TD Szestak Tadge T Lennartz Frank F Higgins Matt K MK Newbold Chris I CI Craig Alister G AG

Scientific reports 20180219 1

The Plasmodium falciparum variant surface antigen PfEMP1 expressed on the surface of infected erythrocytes is thought to play a major role in the pathology of severe malaria. As the sequence pool of the var genes encoding PfEMP1 expands there are opportunities, despite the high degree of sequence diversity demonstrated by this gene family, to reconstruct full-length var genes from small sequence tags generated from patient isolates. To test whether this is possible we have used a set of recently ...[more]

PMID: 29459671

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Project description:BackgroundEukaryotic cellular machineries are intricately regulated by several molecular mechanisms involving transcriptional control, post-translational control and post-translational modifications of proteins (PTMs). Reversible protein phosphorylation/dephosphorylation process, which involves kinases as well as phosphatases, represents an important regulatory mechanism for diverse pathways and systems in all organisms including human malaria parasite, Plasmodium falciparum. Earlier analysis on P. falciparum protein-phosphatome revealed presence of 34 phosphatases in Plasmodium genome. Recently, we re-analysed P. falciparum phosphatome aimed at identifying parasite specific phosphatases.ResultsPlasmodium database (PlasmoDB 9.2) search, combined with PFAM and CDD searches, revealed 67 candidate phosphatases in P. falciparum. While this number is far less than the number of phosphatases present in Homo sapiens, it is almost the same as in other Plasmodium species. These Plasmodium phosphatase proteins were classified into 13 super families based on NCBI CDD search. Analysis of proteins expression profiles of the 67 phosphatases revealed that 44 phosphatases are expressed in both schizont as well as gametocytes stages. Fourteen phosphatases are common in schizont, ring and trophozoite stages, four phosphatases are restricted to gametocytes, whereas another three restricted to schizont stage. The phylogenetic trees for each of the known phosphatase super families reveal a considerable phylogenetic closeness amongst apicomplexan organisms and a considerable phylogenetic distance with other eukaryotic model organisms included in the study. The GO assignments and predicted interaction partners of the parasite phosphatases indicate its important role in diverse cellular processes.ConclusionIn the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes. Intriguingly, amongst these phosphatases, we could identify six Plasmodium specific phosphatases and 33 putative phosphatases that do not have human orthologs, thereby suggesting that these phosphatases have the potential to be explored as novel antimalarial drug targets.

Dataset Information

In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum.

Publications

In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum.

Similar Datasets

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