{"doi":"10.1101/2023.12.26.573373","title":"Stabilization of F-actin by <i>Salmonella</i> effector SipA resembles the structural effects of inorganic phosphate and phalloidin","abstract":"Abstract Entry of Salmonella into host enterocytes strictly relies on its pathogenicity island 1 effector SipA. We found that SipA binds to F-actin in a unique mode in a 1:2 stoichiometry with picomolar affinity. A cryo-EM reconstruction revealed that SipA’s globular core binds at the grove between actin strands, whereas the extended C-terminal arm penetrates deeply into the inter-strand space, stabilizing F-actin from within. The unusually strong binding of SipA is achieved via a combination of fast association via the core and very slow dissociation dictated by the arm. Similarly to P i , BeF 3 , and phalloidin, SipA potently inhibited actin depolymerization by ADF/cofilin, which correlated with the increased filament stiffness, supporting the hypothesis that F-actin’s mechanical properties contribute to the recognition of its nucleotide state by protein partners. The remarkably strong binding to F-actin maximizes the toxin’s effects at the injection site while minimizing global influence on the cytoskeleton and preventing pathogen detection by the host cell.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":415400,"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":0.9529,"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":471696,"name":"Lucas A. Runyan","orcid":"0000-0001-5690-7849","position":1,"is_corresponding":false},{"id":241037,"name":"Elena Kudryashova","orcid":"0000-0002-1646-1229","position":2,"is_corresponding":false},{"id":305492,"name":"Edward H. Egelman","orcid":"0000-0003-4844-5212","position":3,"is_corresponding":false},{"id":241042,"name":"Dmitri S. Kudryashov","orcid":"0000-0003-1782-3305","position":4,"is_corresponding":false},{"id":378345,"name":"E. Niedzialkowska","orcid":"0000-0002-0348-3154","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:22:12.933438Z","pmid":"38234808","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":[]}