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Legionella effector LegA15/AnkH contains an unrecognized cysteine protease-like domain and displays structural similarity to LegA3/AnkD, but differs in host cell localization
Acta Crystallographica Section D ( IF 2.6 ) Pub Date : 2021-11-11 , DOI: 10.1107/s2059798321010469
Ivy Yeuk Wah Chung 1 , Lei Li 1 , Miroslaw Cygler 1
Affiliation  

Legionella pneumophila is a human pathogen that causes Legionnaires' disease, a severe form of pneumonia. It can be found in various aquatic environments ranging from cooling towers to ponds. In addition to causing disease in humans, it can also infect free-living amoebae commonly found in various aquatic environments. Once inside a human lung macrophage, it creates a niche called the Legionella-containing vacuole where it can evade phagolysosomal degradation and replicate. During infection, normal cellular functions are hijacked by proteins that are secreted by the pathogen, called bacterial effectors. Here, the structural characterization of the effector LegA15/AnkD is reported. The protein contains an ankyrin-repeat domain followed by a cysteine protease-like (CPL) domain with a putative catalytic triad consisting of His268–Asn290–Cys361. The CPL domain shows similarity to the CE clan in the MEROPS database, which contains ubiquitin-like hydrolases. The C-terminal segment of LegA15, including the CPL domain, shows structural similarity to another effector, LegA3/AnkH, while they share only 12% sequence identity. When expressed in mammalian cells, LegA15 is localized within the cytoplasm, in contrast to LegA3, which localizes to the nucleus.

中文翻译:

军团菌效应器 LegA15/AnkH 包含一个无法识别的半胱氨酸蛋白酶样结构域,并显示出与 LegA3/AnkD 的结构相似性,但在宿主细胞定位方面不同

嗜肺军团菌是一种人类病原体,可导致军团病,一种严重的肺炎。它可以在从冷却塔到池塘的各种水生环境中找到。除了引起人类疾病外,它还可以感染各种水生环境中常见的自由生活的变形虫。一旦进入人肺巨噬细胞,它就会产生一个称为军团菌的生态位-含有液泡,它可以逃避吞噬溶酶体的降解和复制。在感染期间,正常的细胞功能被病原体分泌的蛋白质(称为细菌效应物)劫持。在这里,报告了效应器 LegA15/AnkD 的结构特征。该蛋白质包含一个锚蛋白重复结构域,然后是一个半胱氨酸蛋白酶样 (CPL) 结构域,其推定的催化三联体由 His268–Asn290–Cys361 组成。CPL 域与 MEROPS 数据库中的 CE 家族相似,其中包含泛素样水解酶。LegA15 的 C 端片段,包括 CPL 域,与另一个效应器 LegA3/AnkH 具有结构相似性,而它们仅具有 12% 的序列同一性。当在哺乳动物细胞中表达时,LegA15 定位于细胞质内,与 LegA3 相比,
更新日期:2021-12-06
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