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Immunosuppressive Yersinia Effector YopM Binds DEAD Box Helicase DDX3 to Control Ribosomal S6 Kinase in the Nucleus of Host Cells
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نویسنده
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berneking l. ,schnapp m. ,rumm a. ,trasak c. ,ruckdeschel k. ,alawi m. ,grundhoff a. ,kikhney a.g. ,koch-nolte f. ,buck f. ,perbandt m. ,betzel c. ,svergun d.i. ,hentschke m. ,aepfelbacher m.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 6
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چکیده
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Yersinia outer protein m (yopm) is a crucial immunosuppressive effector of the plaque agent yersinia pestis and other pathogenic yersinia species. yopm enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. here we identify the dead-box helicase 3 (ddx3) as a novel interaction partner of y. enterocolitica yopm and present the three-dimensional structure of a yopm:ddx3 complex. knockdown of ddx3 or inhibition of the exportin chromosomal maintenance 1 (crm1) increased the nuclear level of yopm suggesting that yopm exploits ddx3 to exit the nucleus via the crm1 export pathway. increased nuclear yopm levels caused enhanced phosphorylation of ribosomal s6 kinase 1 (rsk1) in the nucleus. in y. enterocolitica infected primary human macrophages yopm increased the level of interleukin-10 (il-10) mrna and this effect required interaction of yopm with rsk and was enhanced by blocking yopm's nuclear export. we propose that the ddx3/crm1 mediated nucleocytoplasmic shuttling of yopm determines the extent of phosphorylation of rsk in the nucleus to control transcription of immunosuppressive cytokines. © 2016 berneking et al.
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آدرس
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institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, bioinformatics core,university medical center hamburg-eppendorf,hamburg,germany,heinrich-pette-institute (hpi),leibniz institute for experimental virology,research group virus genomics,hamburg, Germany, heinrich-pette-institute (hpi),leibniz institute for experimental virology,research group virus genomics,hamburg, Germany, european molecular biology laboratory (embl),hamburg outstation,hamburg, Germany, institute of immunology,university medical center,hamburg, Germany, institute of clinical chemistry,university medical center,hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg,germany,institute of biochemistry and molecular biology,university of hamburg,laboratory of structural biology of infection and inflammation,hamburg,germany,the hamburg centre for ultrafast imaging,hamburg, Germany, institute of biochemistry and molecular biology,university of hamburg,laboratory of structural biology of infection and inflammation,hamburg, Germany, european molecular biology laboratory (embl),hamburg outstation,hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany, institute of medical microbiology,virology and hygiene,university medical center hamburg-eppendorf (uke),hamburg, Germany
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Authors
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