4bvu

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Structure of Shigella effector OspG in complex with host UbcH5c- Ubiquitin conjugateStructure of Shigella effector OspG in complex with host UbcH5c- Ubiquitin conjugate

Structural highlights

4bvu is a 3 chain structure with sequence from Homo sapiens and Shigella flexneri. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OSPG_SHIFL Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is a kinase that is involved in down-regulation of the host innate response induced by invasive bacteria. Prevents or at least delays host phospho-NF-kappa-B inhibitor alpha (NFKBIA) degradation. Does not phosphorylate E2 enzymes.[1]

Publication Abstract from PubMed

Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A co-crystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.

E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis.,Pruneda JN, Smith FD, Daurie A, Swaney DL, Villen J, Scott JD, Stadnyk AW, Le Trong I, Stenkamp RE, Klevit RE, Rohde JR, Brzovic PS EMBO J. 2014 Jan 20. PMID:24446487[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Kim DW, Lenzen G, Page AL, Legrain P, Sansonetti PJ, Parsot C. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14046-51. Epub 2005 Sep 14. PMID:16162672 doi:http://dx.doi.org/10.1073/pnas.0504466102
  2. Pruneda JN, Smith FD, Daurie A, Swaney DL, Villen J, Scott JD, Stadnyk AW, Le Trong I, Stenkamp RE, Klevit RE, Rohde JR, Brzovic PS. E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis. EMBO J. 2014 Jan 20. PMID:24446487 doi:http://dx.doi.org/10.1002/embj.201386386

4bvu, resolution 2.70Å

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OCA