5haf
Structure of Salmonella enterica effector protein SseL
Structural highlights
FunctionSSEL_SALTY Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protease targets the host cell ubiquitin pathway by acting as a deubiquitinase in infected host cells. Specifically hydrolyzes mono- and polyubiquitin substrates in vitro with a preference for 'Lys-63'-linked ubiquitin chains, suggesting that it interferes with a signaling pathway rather than inhibiting proteasomal-dependent degradation of its targets. Does not possess desumoylating activity. Is required for the Salmonella-induced delayed cytotoxicity in macrophages and full virulence. Is not required for intracellular bacterial replication.[1] [2] Publication Abstract from PubMedPathogenic bacteria rely on secreted effector proteins to manipulate host signaling pathways, often in creative ways. CE clan proteases, specific hydrolases for ubiquitin-like modifications (SUMO and NEDD8) in eukaryotes, reportedly serve as bacterial effector proteins with deSUMOylase, deubiquitinase, or, even, acetyltransferase activities. Here, we characterize bacterial CE protease activities, revealing K63-linkage-specific deubiquitinases in human pathogens, such as Salmonella, Escherichia, and Shigella, as well as ubiquitin/ubiquitin-like cross-reactive enzymes in Chlamydia, Rickettsia, and Xanthomonas. Five crystal structures, including ubiquitin/ubiquitin-like complexes, explain substrate specificities and redefine relationships across the CE clan. Importantly, this work identifies novel family members and provides key discoveries among previously reported effectors, such as the unexpected deubiquitinase activity in Xanthomonas XopD, contributed by an unstructured ubiquitin binding region. Furthermore, accessory domains regulate properties such as subcellular localization, as exemplified by a ubiquitin-binding domain in Salmonella Typhimurium SseL. Our work both highlights and explains the functional adaptations observed among diverse CE clan proteins. The Molecular Basis for Ubiquitin and Ubiquitin-like Specificities in Bacterial Effector Proteases.,Pruneda JN, Durkin CH, Geurink PP, Ovaa H, Santhanam B, Holden DW, Komander D Mol Cell. 2016 Jul 21;63(2):261-76. doi: 10.1016/j.molcel.2016.06.015. Epub 2016 , Jul 14. PMID:27425412[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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