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...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.展开更多
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.).
文摘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.
