Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
PLoS One. 2011 Jan 20;6(1):e16294. doi: 10.1371/journal.pone.0016294.
Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion.
几种疟原虫的富含色氨酸的蛋白质已被鉴定出来,它们在宿主-寄生虫相互作用中起着重要作用。为了将这些蛋白质开发为治疗靶点,需要对它们进行结构特征描述。在这里,我们描述了一种新的恶性疟原虫富含色氨酸蛋白,命名为 PvTRAg33.5。它在寄生虫的血期表达,其基因包含两个外显子。外显子 1 编码一个 23 个氨基酸长的假定信号肽,很可能被切割掉,而外显子 2 编码 252 个氨基酸的成熟蛋白。成熟蛋白含有 B 细胞表位,在恶性疟原虫感染期间被人体免疫系统识别。PvTRAg33.5 含有 24 个(9.5%)色氨酸残基和 6 个基序,其模式在富含色氨酸的蛋白质中相似。PvTRAg33.5 的模型结构由一个多结构域架构组成,该架构由大量色氨酸残基稳定。重组 PvTRAg33.5 显示出主要的α螺旋结构,在 pH 值低于 4.5 时发生α螺旋到β片层的转变。在中性 pH 值下,温度超过 50°C 时,蛋白质会发生不可逆的非天然状态。在 35%酒精存在下,其二级和三级结构保持稳定,但在更高的酒精浓度下,这些结构会因色氨酸残基之间的疏水相互作用受到干扰而不稳定。在蛋白质转运过程中,蛋白质的这些结构变化可能会发生,以与最终目的地的其他蛋白质相互作用,从而发挥生物功能,如红细胞入侵。