Crystal structure of MvcA-UBE2N-Ub complex from Legionella pneumophilaCrystal structure of MvcA-UBE2N-Ub complex from Legionella pneumophila

Structural highlights

6jky is a 6 chain structure with sequence from Homo sapiens, Legionella pneumophila subsp. pneumophila str. Philadelphia 1 and Schistosoma margrebowiei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.454Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q5ZTL3_LEGPH

Publication Abstract from PubMed

The Legionella pneumophila effector MavC induces ubiquitination of the E2 ubiquitin-conjugating enzyme UBE2N by transglutamination, thereby abolishing its function in the synthesis of K63 -type polyubiquitin chains. The inhibition of UBE2N activity creates a conundrum because this E2 enzyme is important in multiple signaling pathways, including some that are important for intracellular L. pneumophila replication. Here, we show that prolonged inhibition of UBE2N activity by MavC restricts intracellular bacterial replication and that the activity of UBE2N is restored by MvcA, an ortholog of MavC (50% identity) with ubiquitin deamidase activity. MvcA functions to deubiquitinate UBE2N-Ub using the same catalytic triad required for its deamidase activity. Structural analysis of the MvcA-UBE2N-Ub complex reveals a crucial role of the insertion domain in MvcA in substrate recognition. Our study establishes a deubiquitination mechanism catalyzed by a deamidase, which, together with MavC, imposes temporal regulation of the activity of UBE2N during L. pneumophila infection.

Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination.,Gan N, Guan H, Huang Y, Yu T, Fu J, Nakayasu ES, Puvar K, Das C, Wang D, Ouyang S, Luo ZQ EMBO J. 2020 Feb 17;39(4):e102806. doi: 10.15252/embj.2019102806. Epub 2019 Dec, 11. PMID:31825121[1]

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

See Also

References

  1. Gan N, Guan H, Huang Y, Yu T, Fu J, Nakayasu ES, Puvar K, Das C, Wang D, Ouyang S, Luo ZQ. Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination. EMBO J. 2020 Feb 17;39(4):e102806. doi: 10.15252/embj.2019102806. Epub 2019 Dec, 11. PMID:31825121 doi:http://dx.doi.org/10.15252/embj.2019102806

6jky, resolution 2.45Å

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