Complete genome sequencing of the kinetoplastid protozoans Trypanosoma cruzi, Trypanosoma brucei and Leishmania major (Tritryp), published in 2005, opened up new perspectives for drug development targeting Chagas disease, African sleeping sickness and Leishmaniasis, neglected diseases affecting millions of most economically disadvantaged people. Still, half of the Tritryp genes code for proteins of unknown function. Moreover, almost 50% of conserved eukaryotic protein domains are missing in the Tritryp genomes. This suggests that functional and structural characterization of proteins of unknown function could reveal novel protein folds used by the trypanosomes for common cellular processes. Furthermore, proteins without homologous counterparts in humans may provide potential targets for therapeutic intervention. Here we describe the crystal structure of the T. cruzi protein Q4D6Q6, a conserved and kinetoplastid-specific protein essential for cell viability. Q4D6Q6 is a representative of a family of 20 orthologs, all annotated as proteins of unknown function. Q4D6Q6 monomers adopt a ββαββαββ topology and form a propeller-like tetramer. Oligomerization was verified in solution using NMR, SAXS, analytical ultra-centrifugation and gel filtration chromatography. A rigorous search for similar structures using the DALI server revealed similarities with propeller-like structures of several different functions. Although a Q4D6Q6 function could not be inferred from such structural comparisons, the presence of an oxidized cysteine at position 69, part of a cluster with phosphorylated serines and hydrophobic residues, identifies a highly reactive site and suggests a role of this cysteine as a nucleophile in a post-translational modification reaction.

动质体原生动物克氏锥虫、布氏锥虫和利什曼原虫的完整基因组测序(Tritryp) 于 2005 年出版，为针对南美锥虫病、非洲昏睡病和利什曼病等影响数百万经济最弱势人群的被忽视疾病的药物开发开辟了新的前景。尽管如此，仍有一半的 Tritryp 基因编码功能未知的蛋白质。此外，几乎 50% 的保守真核蛋白质结构域在 Tritryp 基因组中缺失。这表明未知功能蛋白质的功能和结构表征可以揭示锥虫用于常见细胞过程的新蛋白质折叠。此外，在人类中没有同源对应物的蛋白质可能为治疗干预提供潜在的靶点。这里我们描述了T. cruzi的晶体结构蛋白质 Q4D6Q6，一种对细胞活力至关重要的保守和动质体特异性蛋白质。Q4D6Q6 是 20 个直向同源物家族的代表，全部注释为功能未知的蛋白质。Q4D6Q6 单体采用 ββαββαββ 拓扑结构并形成螺旋桨状四聚体。使用NMR、SAXS、分析超离心和凝胶过滤色谱法在溶液中验证低聚。使用 DALI 服务器对类似结构的严格搜索揭示了几种不同功能的类似螺旋桨结构的相似之处。虽然不能从这样的结构比较中推断出 Q4D6Q6 的功能，但在第 69 位存在氧化半胱氨酸，这是具有磷酸化丝氨酸和疏水残基的簇的一部分，