{"doi":"10.1016/j.str.2024.12.012","title":"Mg2+-dependent mechanism of environmental versatility in a multidrug efflux pump","abstract":"Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are major drivers of multidrug resistance among gram-negative bacteria. Cations, such as Mg 2+ , become concentrated within the periplasm and, in contrast to the cytoplasm, its pH is sensitive to conditions outside the cell. Here, we reveal an interplay between Mg 2+ and pH in modulating the structural dynamics of the periplasmic adapter protein, AcrA, and its function within the prototypical AcrAB-TolC multidrug pump from Escherichia coli . In the absence of Mg 2+ , AcrA becomes increasingly plastic within acidic conditions, but when Mg 2+ is bound this is ameliorated, resulting instead in domain specific organization. We establish a unique histidine residue directs these dynamics and is essential for sustaining pump activity across acidic, neutral, and basic regimes. Overall, we propose Mg 2+ conserves AcrA structural mobility to ensure optimal AcrAB-TolC function within rapidly changing environments commonly faced during bacterial infection and colonization.","journal":"Structure","year":2025,"id":516857,"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":0.9468,"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":711650,"name":"Muhammad Ramiz Uddin","orcid":"0000-0002-2337-7383","position":1,"is_corresponding":false},{"id":647739,"name":"Katie M. Kuo","orcid":"0009-0001-5682-6173","position":2,"is_corresponding":false},{"id":998580,"name":"Laila M. N. Shah","orcid":"0000-0002-6666-6046","position":3,"is_corresponding":false},{"id":295277,"name":"Nicola J. Harris","orcid":"0000-0001-7049-1253","position":4,"is_corresponding":false},{"id":295278,"name":"Paula J. Booth","orcid":"0000-0003-3893-360X","position":5,"is_corresponding":false},{"id":980512,"name":"Dietmar Hammerschmid","orcid":"0000-0002-0210-3690","position":6,"is_corresponding":false},{"id":98033,"name":"James C. Gumbart","orcid":"0000-0002-1510-7842","position":7,"is_corresponding":false},{"id":274353,"name":"Helen I. Zgurskaya","orcid":"0000-0001-8929-4727","position":8,"is_corresponding":false},{"id":998581,"name":"Eamonn Reading","orcid":"0000-0001-8219-0052","position":9,"is_corresponding":false},{"id":998579,"name":"Benjamin Russell Lewis","orcid":"0000-0002-0248-6177","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39809273","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":[]}