{"doi":"10.7554/elife.106975.2.sa1","title":"Reviewer #2 (Public review): Cryo-EM structure revealed a novel F-actin binding motif in a Legionella pneumophila lysine fatty-acyltransferase","abstract":"Legionella pneumophila is an opportunistic bacterial pathogen that causes Legionnaires’ disease. To establish an intracellular niche conducive to replication, L. pneumophila translocates a diverse array of effector proteins that manipulate various host cellular processes, including the actin cytoskeleton. In a screen for effectors that alter actin dynamics, we identified a Legionella effector, Lfat1 (lpg1387), which colocalizes with the actin cytoskeleton in eukaryotic cells. Lfat1 specifically binds F-actin through a novel actin-binding domain (ABD). High-resolution cryo-electron microscopy (cryoEM) analysis revealed that this ABD forms a long α-helix hairpin, with its tip interacting with subdomains I and II of two adjacent actin molecules within the F-actin filament. Interestingly, while individual α-helices of the hairpin fail to bind F-actin, co-expression as separate fusion proteins restores binding activity. Furthermore, we demonstrated that Lfat1 exhibits lysine fatty-acyltransferase (KFAT) activity, targeting host small GTPases. These findings establish a foundation for studying the KFAT family of bacterial toxins and uncover a novel F-actin binding motif, providing an alternative F-actin marker with notable flexibility.","journal":null,"year":2025,"id":587805,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":277252,"name":"Garrison Komaniecki","orcid":"0000-0002-1157-2667","position":1,"is_corresponding":false},{"id":1190897,"name":"Jiaze Liu","orcid":null,"position":2,"is_corresponding":false},{"id":273804,"name":"Hening Lin","orcid":"0000-0002-0255-2701","position":3,"is_corresponding":false},{"id":456611,"name":"Yuxin Mao","orcid":"0000-0002-5064-1397","position":4,"is_corresponding":false},{"id":1473483,"name":"Wenjie W Zeng","orcid":"0000-0003-1028-7845","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":null,"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":[]}