The phylogenetically divergent spirochete bacterium Treponema pallidum subsp. pallidum is the causative agent of syphilis. Central to the capacity of T. pallidum to establish infection is the ability of the pathogen to attach to a diversity of host cells. Many pathogenic bacteria employ leucine‐rich repeat (LRR) domain‐containing proteins to mediate protein–protein interactions, including attachment to host components and establishment of infection. Intriguingly, T. pallidum expresses only one putative LRR domain‐containing protein (Tp0225) with an unknown function. In an effort to ascribe a function to Tp0225, a comprehensive phylogenetic analysis was first performed; this investigation revealed that Tp0225 clusters with the pathogenic clade of treponemes. Its crystal structure was then determined to 2.0 Å resolution using Pt SAD phasing, which revealed a noncanonical architecture containing a hexameric LRR core with a discontinuous β‐sheet bridged by solvent molecules. Furthermore, a surface‐exposed, hydrophobic pocket, which was found in Tp0225 but is largely absent in canonical LRR domains from other pathogenic bacteria, may serve to coordinate a hydrophobic ligand. Overall, this study provides the first structural characterization of the sole LRR domain‐containing protein from T. pallidum and offers insight into the unique molecular landscape of this important human pathogen.

中文翻译：

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梅毒螺旋体 Tp0225 的结构表征揭示了意想不到的富含亮氨酸的重复结构。


系统发育上不同的螺旋体细菌梅毒螺旋体亚种。梅毒是梅毒的病原体。梅毒螺旋体建立感染能力的核心是病原体附着于多种宿主细胞的能力。许多病原菌利用富含亮氨酸重复（LRR）结构域的蛋白质来介导蛋白质-蛋白质相互作用，包括附着于宿主成分和建立感染。有趣的是，梅毒螺旋体只表达一种推定的含有 LRR 结构域的蛋白质 (Tp0225)，其功能未知。为了确定 Tp0225 的功能，首先进行了全面的系统发育分析；这项研究表明，Tp0225 与密螺旋体的致病分支聚集在一起。然后使用 Pt SAD 定相将其晶体结构确定为 2.0 Å 分辨率，揭示了一种非规范结构，其中包含六聚体 LRR 核和由溶剂分子桥接的不连续 β 片层。此外，在 Tp0225 中发现的表面暴露的疏水口袋，但在其他病原菌的典型 LRR 结构域中基本上不存在，可能有助于协调疏水配体。总体而言，这项研究首次提供了来自梅毒螺旋体的唯一含有 LRR 结构域的蛋白质的结构特征，并深入了解了这种重要人类病原体的独特分子景观。