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作 者:Jiajia Gao Wenwen Xu Feng Tang Minrui Xu Qin Zhou Xingyuan Yang Nannan Zhang Jinming Ma Qi Yang Xiaofang Chen Ximing Qin Honghua Ge
机构地区:[1]Institute of Health Sciences and Technology,Institutes of Material Science and Information Technology,Anhui University,Hefei 230601,China [2]School of Life Sciences,Anhui University,Hefei 230601,China [3]Information Materials and Intelligent Sensing Laboratory of Anhui Province,Anhui University,Hefei 230601,China
出 处:《Journal of Molecular Cell Biology》2023年第5期52-65,共14页分子细胞生物学报(英文版)
基 金:supported by grants from the National Natural Science Foundation of China(31970103 to H.G.and 32071158 to X.Q.);China Postdoctoral Science Foundation(2021M700178 to X.C.);the Natural Science Foundation of Department of Education of Anhui Province(K120462017 to X.C.).
摘 要: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.
关 键 词:Lamin-B2 Importin-13 cell death Legionella pneumophila SidN Lpg1083 T4SS effector
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