BACKGROUND The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. RESULTS This study characterizes the structures of the soluble domains of two conserved core ESX-1 components - EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD1has a ubiquitin-like fold and forms a dimer with a negatively charged groove. CONCLUSIONS These structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.

中文翻译：

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EccB1和EccD1的结构来自分枝杆菌ESX-1 VII型分泌系统的核心复合物。

背景技术ESX-1 VII型分泌系统是致病性分枝杆菌（包括结核分枝杆菌）中毒力的重要决定因素。这种复杂的分子机器通过分枝杆菌细胞的包膜分泌折叠的蛋白质，从而破坏了宿主的免疫反应。尽管它在疾病中起重要作用，但对ESX-1分泌系统的分子结构知之甚少。结果这项研究表征了两个保守的核心ESX-1组件-EccB1和EccD1的可溶性结构域的结构。EccB1的周质结构域由4个重复结构域和一个中央结构域组成，它们共同形成一个准2倍对称结构。EccB1的重复域在结构上与已知的肽聚糖结合蛋白相似，表明在将ESX-1系统锚定在周质空间中的作用。EccD1的胞质域具有泛素样折叠，并形成带有负电荷凹槽的二聚体。结论这些结构代表了解决整个ESX-1组装体分子结构的重要一步，可能有助于以ESX-1为目标的结核病干预策略。