{"doi":"10.1101/2023.08.10.552793","title":"Bacterial Shedu immune nucleases share a common enzymatic core regulated by diverse sensor domains","abstract":"Summary Prokaryotes encode diverse anti-bacteriophage immune systems, including the single-protein Shedu nuclease. Here we reveal the structural basis for activation of Bacillus cereus Shedu. In the inactive homotetramer, a key catalytic residue in Shedu’s nuclease domain is sequestered away from the catalytic site. Activation involves a conformational change that completes the active site and promotes assembly of a homo-octamer for coordinated double-strand DNA cleavage. Removal of Shedu’s N-terminal domain ectopically activates the enzyme, suggesting that this domain allosterically inhibits Shedu in the absence of infection. Bioinformatic analysis of nearly 8,000 Shedu homologs reveals remarkable diversity in their N-terminal regulatory domains: we identify 79 domain families falling into eight functional classes, including diverse nucleic acid binding, enzymatic, and other domains. Together, these data reveal Shedu as a broad family of immune nucleases with a common nuclease core regulated by diverse N-terminal domains that likely respond to a range of infection-related signals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391060,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1163344,"name":"Huan Li","orcid":"0000-0003-0973-9955","position":1,"is_corresponding":false},{"id":847687,"name":"Amar Deep","orcid":"0000-0003-2003-2889","position":2,"is_corresponding":false},{"id":735343,"name":"Eray Enüstün","orcid":"0000-0001-7550-7752","position":3,"is_corresponding":false},{"id":286505,"name":"Dapeng Zhang","orcid":"0000-0001-8535-7620","position":4,"is_corresponding":false},{"id":106560,"name":"Kevin D. Corbett","orcid":"0000-0001-5854-2388","position":5,"is_corresponding":false},{"id":847688,"name":"Yajie Gu","orcid":"0000-0002-1514-1477","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"37609250","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":[]}