Despite a significant drop in malaria deaths during the past decade, malaria continues to be one of the biggest health problems around the globe. WD40 repeats (WDRs) containing proteins comprise one of the largest and functionally diverse protein superfamily in eukaryotes, acting as scaffolds for assembling large protein complexes. In the present study, we report an extensive in silico analysis of the WDR gene family in human malaria parasite Plasmodium falciparum. Our genome-wide identification has revealed 80 putative WDR genes in P. falciparum (PfWDRs). Five distinct domain compositions were discovered in Plasmodium as compared to the human host. Notably, 31 PfWDRs were annotated/re-annotated on the basis of their orthologs in other species. Interestingly, most PfWDRs were larger as compared to their human homologs highlighting the presence of parasite-specific insertions. Fifteen PfWDRs appeared specific to the Plasmodium with no assigned orthologs. Expression profiling of PfWDRs revealed a mixture of linear and nonlinear relationships between transcriptome and proteome, and only nine PfWDRs were found to be stage-specific. Homology modeling identified conservation of major binding sites in PfCAF-1 and PfRACK. Protein-protein interaction network analyses suggested that PfWDRs are highly connected proteins with ~1928 potential interactions, supporting their role as hubs in cellular networks. The present study highlights the roles and relevance of the WDR family in P. falciparum, and identifies unique features that lay a foundation for further experimental dissection of PfWDRs.
Malaria is a devastating disease affecting millions of lives in tropical and subtropical countries since ages. Despite significant reduction in malaria cases since 2010, malaria continues to be one of the major infectious diseases. Malaria elimination efforts are hampered with the emergence of multidrug resistant strains. The most promising vaccine candidate against malaria is RTS,S that showed an efficacy of 39-50%. The development of efficient vaccine remains elusive because of parasite multistage life cycle and antigenic variation. Global efforts are underway to eradicate malaria and there is significant progress in fight against malaria with many countries certified malaria free during last five years. The recent addition to this list is Algeria and Argentina and China is heading forward to be malaria free with no indigenous malaria case. However, rapid development of drug resistance strains highlights requirements of more efforts to defeat the pathogen.
Conclusion:This study presents preliminary characterization of a type III Hsp40 co-chaperone of the parasite. Further functional characterization of this putative multifunctional chaperone would undoubtedly provide an insight in parasite molecular biology for the development of novel antimalarials.
Histones N-terminal tails are the sites for Post-Translational Modifications (PTMs) that regulate the chromatin structure, thus chromatin associated processes. PTMs include methylation, acetylation, phosphorylation, ubiquitination, sumoylation, and ribosylation. Histone lysine methylation is associated with both transcription activation and repression. The SET domain proteins carry out the histone lysine methylation on the N-terminal tails of histones H3 and H4 and are called Histone Lysine Methyltransferases (HKMTs). A total of ten SET domain genes have been identified in human malarial parasite Plasmodium falciparum. The present study provides detailed computational analysis of P. falciparum SET domain proteins (PfSETs). The analyses cover PfSET family in terms of domain composition, physiochemical properties, subcellular localization, expression profiling and phylogenetic relationships. The work also highlights the conservation of important catalytic residues in PfSETs. The present study provides a detailed insight into the PfSET family, thus opens a platform for further developments.
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