Structural highlights
Function
SDEA_LEGPH Secreted effector that interferes with the host cell ubiquitin pathway and is required for intracellular bacterial replication. Catalyzes the ubiquitination of several mammalian Rab proteins (Rab33b, Rab1, Rab6a and Rab30) during L.pneumophila infection, without engaging the standard cellular enzyme cascade (E1 and E2). Transfers an ADP-ribose moiety from NAD to the 'Arg-42' residue of ubiquitin in a reaction that releases nicotinamide. The modified ubiquitin is subsequently transferred to the substrate protein through an unknown mechanism that results in the release of AMP. Cannot ubiquitinate the endosomal Rab5 or the cytoskeletal small GTPase Rac1 (PubMed:27049943). Also acts as a deubiquitinase (DUB), catalyzing the cleavage of three of the most abundant polyubiquitin chains ('Lys-11', 'Lys-48' and 'Lys-63') with a distinct preference for 'Lys-63' linkages; is thus able to efficiently remove 'Lys-63'-linked polyubiquitin chains from the phagosomal surface. Is also able to remove NEDD8 from neddylated proteins, but is unable to recognize SUMO. The DUB activity of SdeA is important for regulating the dynamics of ubiquitin association with the bacterial phagosome, but is dispensable for its role in intracellular bacterial replication (PubMed:26598703).[1] [2]
References
- ↑ Sheedlo MJ, Qiu J, Tan Y, Paul LN, Luo ZQ, Das C. Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination. Proc Natl Acad Sci U S A. 2015 Nov 23. pii: 201514568. PMID:26598703 doi:http://dx.doi.org/10.1073/pnas.1514568112
- ↑ Qiu J, Sheedlo MJ, Yu K, Tan Y, Nakayasu ES, Das C, Liu X, Luo ZQ. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors. Nature. 2016 May 5;533(7601):120-4. doi: 10.1038/nature17657. Epub 2016 Apr 6. PMID:27049943 doi:http://dx.doi.org/10.1038/nature17657
