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TitleImmunosuppressive Yersinia Effector YopM Binds DEAD Box Helicase DDX3 to Control Ribosomal S6 Kinase in the Nucleus of Host Cells.
Journal, issue, pagesPLoS Pathog, Vol. 12, Issue 6, Page e1005660, Year 2016
Publish dateJun 14, 2016
AuthorsLaura Berneking / Marie Schnapp / Andreas Rumm / Claudia Trasak / Klaus Ruckdeschel / Malik Alawi / Adam Grundhoff / Alexey G Kikhney / Friedrich Koch-Nolte / Friedrich Buck / Markus Perbandt / Christian Betzel / Dmitri I Svergun / Moritz Hentschke / Martin Aepfelbacher /
PubMed AbstractYersinia 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 ...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.
External linksPLoS Pathog / PubMed:27300509 / PubMed Central
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution3.2 Å
Structure data

SASDAU8:
Immunosuppressive virulence protein YopM (Yersinia outer protein M (34-481), YopM)
Method: SAXS/SANS

SASDAV8:
DEAD box helicase DDX3 (DEAD box RNA helicase DDX3 (51-418), DDX3)
Method: SAXS/SANS

SASDAW8:
2:1 YopM:DDX3 complex (Yersinia outer protein M (34-481), YopM + DEAD box RNA helicase DDX3 (51-418), DDX3)
Method: SAXS/SANS

PDB-4ow2:
YopM from Yersinia enterocolitica WA-314
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • Yersinia enterocolitica (bacteria)
  • yersinia enterocolitica subsp. enterocolitica wa-314 (bacteria)
KeywordsTOXIN / leucine-rich repeat / LRR

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