title: Characterisation of the gene encoding an unusually divergent TATA-binding protein (TBP) from the extremely A+T-rich human malaria parasite Plasmodium falciparum.
abstract: The intergenic regions of the human malaria parasite, Plasmodium falciparum, are extreme in their base composition, averaging approx. 90% A + T. As a first step to investigating whether transcription in this organism follows conventional models based largely on yeast, we have isolated and characterised the gene (TBP) encoding its TATA-binding protein (TBP). The gene is present as a single copy on chromosome 5 and is expressed as a 1.8-kb mRNA encoding a protein of 228 amino acids (aa) (26 164 Da). The inferred protein product has a bipartite structure consisting of a 45-aa species-specific N-terminal domain and a 183-aa C-terminal domain. In the latter, the malarial protein contains two directly repeated, but imperfectly homologous regions, each approx. 78 aa in length, together with a highly basic region located between them. These features are characteristic of all TBPs studied to date. Moreover, hydropathy plots suggest that the overall folding of this C-terminal domain is very similar to that of other TBPs. However, TBP from P. falciparum is much less closely related at the primary sequence level to the archetypal yeast homologue than are all other characterised TBPs (42% identity, compared to 76-93%, respectively). Despite this divergence of the primary sequence, most residues known to be involved in DNA binding are conserved. Those instances where sequence variation at generally conserved residues is observed may reflect functional differences that could ultimately be exploited by selective chemotherapy.
authors.affiliation: Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology, UK.
authors.forename: M B
authors.initials: MB
authors.lastname: McAndrew
authors.forename: M
authors.initials: M
authors.lastname: Read
authors.forename: P F
authors.initials: PF
authors.lastname: Sims
authors.forename: J E
authors.initials: JE
authors.lastname: Hyde
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002874:Chromosome Mapping; D016054:DNA, Protozoan; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors