The Apicomplexan AP2 family: integral factors regulating Plasmodium development

Abstract

Malaria is caused by protozoan parasites of the genus Plasmodium and involves infection of multiple hosts and cell types during the course of an infection. To complete its complex life cycle the parasite requires strict control of gene regulation for survival and successful propagation. Thus far, the Apicomplexan AP2 (ApiAP2) family of DNA-binding proteins is the sole family of proteins to have surfaced as candidate transcription factors in all apicomplexan species. Work from several laboratories is beginning to shed light on how the ApiAP2 proteins from Plasmodium spp. contribute to the regulation of gene expression at various stages of parasite development. Here we highlight recent progress toward understanding the role of Plasmodium ApiAP2 proteins in DNA related regulatory processes including transcriptional regulation and gene silencing.

Figure 1. Conservation, motifs, structure and binding sites of Plasmodium AP2 domains

The top panel lists the gene IDs and DNA motifs for each P. falciparum AP2 domain. The best match for each domain in the other Plasmodium species was determined by BLAST results for each individual domain. The presence of an orthologue in P. reichenowi is based on contig evidence from partial genome shotgun sequencing by the Wellcome Trust Sanger Institute. Purple shading indicates a viable knock-out exists based on data from ‡ [40], ∂ [41], ψ [39], and § [38]. Motifs taken from * [42], † [37], Φ[28], ψ [39], § [38]; ND indicates no motif has been found to date. ∂ The PF07_0126 motif is only observed when both domains are present in tandem. The bottom left panel shows a model of the crystal structure of the PF14_0633 AP2 domain [27]. Individual monomers are shown in blue and red, which demonstrates that the helix is swapped between the two domains. The bottom right panel shows the distribution of four P. falciparum AP2 motifs on chromosome 4. Binding sites for PF14_0633, PF13_0235_D1 and PF11_0442 are based on predictions from [42], and the SPE2 chromatin immunoprecipitation data (ChIP-chip) was taken from [37]. PF14_0633 and PF11_442 have been demonstrated to function as transcription factors [38, 39] and their motifs are distributed across the entire chromosome. Conversely the SPE2 binding sites are restricted to chromosome ends and serve as DNA tethering sites [37].