{"doi":"10.1038/s41467-024-46649-2","title":"Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain","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.","journal":"Nature Communications","year":2024,"id":432069,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395229,"name":"Jiaqi Fu","orcid":"0000-0003-0081-6133","position":1,"is_corresponding":false},{"id":289465,"name":"J.G.M. Rack","orcid":"0000-0001-8341-6439","position":2,"is_corresponding":false},{"id":678736,"name":"Chuang Li","orcid":"0000-0002-0271-1397","position":3,"is_corresponding":false},{"id":1237146,"name":"Jim Voorneveld","orcid":null,"position":4,"is_corresponding":false},{"id":618533,"name":"Dmitri V. Filippov","orcid":"0000-0002-6978-7425","position":5,"is_corresponding":false},{"id":263641,"name":"Ivan Ahel","orcid":"0000-0002-9446-3756","position":6,"is_corresponding":false},{"id":395235,"name":"Zhao‐Qing Luo","orcid":"0000-0001-8890-6621","position":7,"is_corresponding":false},{"id":467716,"name":"Chittaranjan Das","orcid":"0000-0002-0567-7753","position":8,"is_corresponding":false},{"id":1153818,"name":"Zhengrui Zhang","orcid":"0000-0003-4566-5199","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:59:35.267142Z","pmid":"38503748","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}