The bacterial effector SidN/Lpg1083 promotes cell death by targeting Lamin-B2.

IF 5.3 2区 生物学 Q2 CELL BIOLOGY Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI:10.1093/jmcb/mjad036
Jiajia Gao, Wenwen Xu, Feng Tang, Minrui Xu, Qin Zhou, Xingyuan Yang, Nannan Zhang, Jinming Ma, Qi Yang, Xiaofang Chen, Ximing Qin, Honghua Ge
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Abstract

To facilitate survival, replication, and dissemination, the intracellular pathogen Legionella pneumophila relies on its unique type IVB secretion system (T4SS) to deliver over 330 effectors to hijack host cell pathways in a spatiotemporal manner. The effectors and their host targets are largely unexplored due to their low sequence identity to the known proteins and functional redundancy. The T4SS effector SidN (Lpg1083) is secreted into host cells during the late infection period. However, to the best of our knowledge, the molecular characterization of SidN has not been studied. Herein, we identified SidN as a nuclear envelope-localized effector. Its structure adopts a novel fold, and the N-terminal domain is crucial for its specific subcellular localization. Furthermore, we found that SidN is transported by eukaryotic karyopherin Importin-13 into the nucleus, where it attaches to the N-terminal region of Lamin-B2 to interfere with the integrity of the nuclear envelope, causing nuclear membrane disruption and eventually cell death. Our work provides new insights into the structure and function of an L. pneumophila effector protein, and suggests a potential strategy utilized by the pathogen to promote host cell death and then escape from the host for secondary infection.

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细菌效应物 SidN/Lpg1083 通过靶向 Lamin-B2 促进细胞死亡。
为了促进生存、复制和传播,细胞内病原体嗜肺军团菌依靠其独特的 IVB 型分泌系统(T4SS)提供 330 多种效应物,以时空方式劫持宿主细胞通路。由于这些效应子及其宿主靶标与已知蛋白质的序列同一性较低,且存在功能冗余,因此它们在很大程度上尚未被研究。T4SS效应子SidN(Lpg1083)在感染后期被分泌到宿主细胞中。然而,据我们所知,SidN 的分子特征尚未得到研究。在此,我们发现 SidN 是一种定位在核膜上的效应物。它的结构采用了一种新的折叠,N-末端结构域对其特异性亚细胞定位至关重要。此外,我们还发现,SidN被真核生物核糖体蛋白Importin-13运输到细胞核中,在那里它附着在Lamin-B2的N端区域,干扰核包膜的完整性,导致核膜破坏,最终导致细胞死亡。我们的研究为了解嗜肺病毒效应蛋白的结构和功能提供了新的视角,并提出了病原体促进宿主细胞死亡,然后逃离宿主进行二次感染的潜在策略。
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来源期刊
CiteScore
9.60
自引率
1.80%
发文量
1383
期刊介绍: The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.
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