8ux2
From Proteopedia
Chromobacterium violaceum mono-ADP-ribosyltransferase CteC in complex with NAD+
Structural highlights
FunctionCTEC_CHRVO ADP-ribosyltransferase that specifically modifies host ubiquitin on 'Thr-66' residue, which causes the shutdown of polyubiquitin synthesis and disrupts the recognition and reversal of polyubiquitin in host cells during infection (PubMed:32330457). Threonine ADP-ribosylation of ubiquitin prevents the transfer of ubiquitin from ubiquitin-activating enzyme E1 to ubiquitin-conjugating enzyme E2, which inhibits subsequent ubiquitin activation and leads to the shutdown of polyubiquitin synthesis in host cells (PubMed:32330457). The modification also causes dysfunction of polyubiquitin chains in cells, thereby blocking host ubiquitin signaling (PubMed:32330457). ADP-ribosylation by CteC is likely irreversible (PubMed:32330457). Plays a crucial role in bacterial colonization in mice during infection (PubMed:32330457).[1] Publication Abstract from PubMedADP-ribosylation is a post-translational modification involved in regulation of diverse cellular pathways. Interestingly, many pathogens have been identified to utilize ADP-ribosylation as a way for host manipulation. A recent study found that CteC, an effector from the bacterial pathogen Chromobacterium violaceum, hinders host ubiquitin signaling pathways via installing mono-ADP-ribosylation on threonine 66 of ubiquitin. However, the molecular basis of substrate recognition by CteC is not well-understood. In this paper, we probed the substrate specificity of this effector at protein and residue levels. We also determined the crystal structure of CteC in complex with NAD(+), which revealed a canonical mono-ADP-ribosyltransferase fold with an additional insertion domain. The AlphaFold predicted model differed significantly from the experimentally determined structure, even in regions not used in crystal packing. Biochemical and biophysical studies indicated unique features of the NAD(+) binding pocket, while showing selectivity distinction between ubiquitin and structurally close ubiquitin-like modifiers and the role of the insertion domain in substrate recognition. Together, this study provides insights into the enzymatic specificities and the key structural features of a novel bacterial ADP-ribosyltransferase involved in host-pathogen interaction. Crystal structure of bacterial ubiquitin ADP-ribosyltransferase CteC reveals a substrate-recruiting insertion.,Zhang Z, Rondon-Cordero HM, Das C J Biol Chem. 2023 Dec 28:105604. doi: 10.1016/j.jbc.2023.105604. PMID:38159861[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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