| Structural highlights
Function
CTEC_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 PubMed
Ubiquitination plays essential roles in eukaryotic cellular processes. The effector protein CteC from Chromobacterium violaceum blocks host ubiquitination by mono-ADP-ribosylation of ubiquitin (Ub) at residue T66. However, the structural basis for this modification is unknown. Here we report three crystal structures of CteC in complexes with Ub, NAD(+) or ADP-ribosylated Ub, which represent different catalytic states of CteC in the modification. CteC adopts a special 'D-E' catalytic motif for catalysis and binds NAD(+) in a half-ligand binding mode. The specific recognition of Ub by CteC is determined by a relatively separate Ub-targeting domain and a long loop L6, not the classic ADP-ribosylating turn-turn loop. Structural analyses with biochemical results reveal that CteC represents a large family of poly (ADP-ribose) polymerase (PARP)-like ADP-ribosyltransferases, which harbors chimeric features from the R-S-E and H-Y-E classes of ADP-ribosyltransferases. The family of CteC-like ADP-ribosyltransferases has a common 'D-E' catalytic consensus and exists extensively in bacteria and eukaryotic microorganisms.
Molecular basis of threonine ADP-ribosylation of ubiquitin by bacterial ARTs.,Tan J, Xu Y, Wang X, Yan F, Xian W, Liu X, Chen Y, Zhu Y, Zhou Y Nat Chem Biol. 2024 Apr;20(4):463-472. doi: 10.1038/s41589-023-01475-3. Epub 2023 , Nov 9. PMID:37945894[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yan F, Huang C, Wang X, Tan J, Cheng S, Wan M, Wang Z, Wang S, Luo S, Li A, Guo X, Feng M, Liu X, Zhu Y, Zhou Y. Threonine ADP-Ribosylation of Ubiquitin by a Bacterial Effector Family Blocks Host Ubiquitination. Mol Cell. 2020 May 21;78(4):641-652.e9. doi: 10.1016/j.molcel.2020.03.016. Epub, 2020 Apr 23. PMID:32330457 doi:http://dx.doi.org/10.1016/j.molcel.2020.03.016
- ↑ Tan J, Xu Y, Wang X, Yan F, Xian W, Liu X, Chen Y, Zhu Y, Zhou Y. Molecular basis of threonine ADP-ribosylation of ubiquitin by bacterial ARTs. Nat Chem Biol. 2023 Nov 9. PMID:37945894 doi:10.1038/s41589-023-01475-3
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