8UX2

Chromobacterium violaceum mono-ADP-ribosyltransferase CteC in complex with NAD+

Summary for 8UX2

• Entry DOI: 10.2210/pdb8ux2/pdb
• Descriptor: NAD(+)--protein-threonine ADP-ribosyltransferase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: mono-adp-ribosyltransferase, adp-ribosylation, bacterial effector, transferase
• Biological source: Chromobacterium violaceum
• Total number of polymer chains: 3
• Total formula weight: 84914.08

Authors

Zhang, Z.,Rondon, H.,Das, C. (deposition date: 2023-11-08, release date: 2024-01-17, Last modification date: 2024-10-16)

Primary citation

Zhang, Z.,Rondon-Cordero, H.M.,Das, C.
Crystal structure of bacterial ubiquitin ADP-ribosyltransferase CteC reveals a substrate-recruiting insertion.
J.Biol.Chem., 300:105604-105604, 2023

PubMed Abstract: ADP-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 (Ub) signaling pathways via installing mono-ADP-ribosylation on threonine 66 of Ub. However, the molecular basis of substrate recognition by CteC is not well understood. In this article, 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 Ub and structurally close Ub-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.

PubMed: 38159861
DOI: 10.1016/j.jbc.2023.105604

Experimental method

X-RAY DIFFRACTION (1.87 Å)