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Publication Abstract from PubMed

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, we reveal that the L. pneumophila effectors MavC (Lpg2147) and MvcA (Lpg2148) are structural homologs 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 approximately Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-kappaB 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.

Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila.,Valleau D, Quaile AT, Cui H, Xu X, Evdokimova E, Chang C, Cuff ME, Urbanus ML, Houliston S, Arrowsmith CH, Ensminger AW, Savchenko A Cell Rep. 2018 Apr 10;23(2):568-583. doi: 10.1016/j.celrep.2018.03.060. PMID:29642013^[1]

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