title: Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.
abstract: 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.
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Chahar
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: Manjeri
authors.initials: M
authors.lastname: Kaushik
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: Sarvajeet Singh
authors.initials: SS
authors.lastname: Gill
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Gakhar
authors.affiliation: DRDO-BU Centre for Life Sciences, Bharathiar University Campus, Coimbatore, Tamil Nadu, India.
authors.forename: Natrajan
authors.initials: N
authors.lastname: Gopalan
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Datt
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Gill
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D020869:Gene Expression Profiling; D017125:Genes, Protozoan; D016678:Genome; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology*; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D010271:Parasites / Q000235:genetics* / Q000254:growth & development; D010802:Phylogeny; D020161:Physical Chromosome Mapping; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D040681:Structural Homology, Protein; D013347:Subcellular Fractions / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D020543:Proteome; D015800:Protozoan Proteins; D012333:RNA, Messenger