8DMP

Crystal structure of Legionella pneumophila macrodomain effector MavL

Summary for 8DMP

• Entry DOI: 10.2210/pdb8dmp/pdb
• Descriptor: MavL (2 entities in total)
• Functional Keywords: macrodomain, effector, glycohydrolase, antitoxin
• Biological source: Legionella pneumophila
• Total number of polymer chains: 8
• Total formula weight: 353445.31

Authors

Zhang, Z.,Das, C. (deposition date: 2022-07-08, release date: 2023-07-12, Last modification date: 2024-07-24)

Primary citation

Zhang, Z.,Fu, J.,Rack, J.G.M.,Li, C.,Voorneveld, J.,Filippov, D.V.,Ahel, I.,Luo, Z.Q.,Das, C.
Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain.
Nat Commun, 15:2452-2452, 2024

PubMed Abstract: ADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of ADP-ribosylation requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being a major family in this category. The pathogen Legionella pneumophila mediates atypical ubiquitination of host targets using the SidE effector family in a process that involves ubiquitin ADP-ribosylation on arginine 42 as an obligatory step. Here, we show that the Legionella macrodomain effector MavL regulates this pathway by reversing the arginine ADP-ribosylation, likely to minimize potential detrimental effects caused by the modified ubiquitin. We determine the crystal structure of ADP-ribose-bound MavL, providing structural insights into recognition of the ADP-ribosyl group and catalytic mechanism of its removal. Further analyses reveal DUF4804 as a class of MavL-like macrodomain enzymes whose representative members show unique selectivity for mono-ADP-ribosylated arginine residue in synthetic substrates. We find such enzymes are also present in eukaryotes, as exemplified by two previously uncharacterized (ADP-ribosyl)hydrolases in Drosophila melanogaster. Crystal structures of several proteins in this class provide insights into arginine specificity and a shared mode of ADP-ribose interaction distinct from previously characterized macrodomains. Collectively, our study reveals a new regulatory layer of SidE-catalyzed ubiquitination and expands the current understanding of macrodomain enzymes.

PubMed: 38503748
DOI: 10.1038/s41467-024-46649-2

Experimental method

X-RAY DIFFRACTION (2.17 Å)