Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila

Journal Article · Sun Apr 01 00:00:00 EDT 2018 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2018.03.060· OSTI ID:1630364

Valleau, Dylan; Quaile, Andrew T.; Cui, Hong; Xu, Xiaohui; Evdokimova, Elena; Chang, Changsoo; Cuff, Marianne E.; Urbanus, Malene L.; Houliston, Scott; Arrowsmith, Cheryl H.; Ensminger, Alexander W.; Savchenko, Alexei

Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called "effectors,'' into host cells during infection, enabling L. pneumophila to establish a replicative niche inside diverse amebas and human macrophages. Here in this paper, we reveal that the L. pneumophila effectors MavC (Lpg2147) and MvcA (Lpg2148) are structural homo-logs of cycle inhibiting factor (Cif) effectors and that the adjacent gene, lpg2149, produces a protein that directly inhibits their activity. In contrast to canonical Cifs, both MavC and MvcA contain an insertion domain and deamidate the residue Gln40 of ubiquitin but not Gln40 of NEDD8. MavC and MvcA are functionally diverse, with only MavC interacting with the human E2-conjugating enzyme UBE2N (Ubc13). MavC deamidates the UBE2N similar to Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-kappa B signaling. Combined, our data reveal a molecular mechanism of host manipulation by pathogenic bacteria and highlight the complex regulatory mechanisms integral to L. pneumophila's pathogenic strategy.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Canadian Institutes of Health Research (CIHR); Canada Foundation for Innovation (CFI); Ontario Research Fund
• Grant/Contract Number: AC02-06CH11357; GM074942; GM094585; MOP-133406
• OSTI ID: 1630364
• Alternate ID(s): OSTI ID: 1465136
• Journal Information: Cell Reports, Journal Name: Cell Reports Vol. 23 Journal Issue: 2; ISSN 2211-1247
• Publisher: Elsevier
• Country of Publication: Netherlands
• Language: English

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59 BASIC BIOLOGICAL SCIENCES