{"doi":"10.1002/pro.2764","title":"Heavy metal transport by the <scp>C</scp>us<scp>CFBA</scp> efflux system","abstract":"<jats:title>Abstract</jats:title><jats:p>It is widely accepted that the increased use of antibiotics has resulted in bacteria with developed resistance to such treatments. These organisms are capable of forming multi‐protein structures that bridge both the inner and outer membrane to expel diverse toxic compounds directly from the cell. Proteins of the resistance nodulation cell division (RND) superfamily typically assemble as tripartite efflux pumps, composed of an inner membrane transporter, a periplasmic membrane fusion protein, and an outer membrane factor channel protein. These machines are the most powerful antimicrobial efflux machinery available to bacteria. In <jats:italic>Escherichia coli,</jats:italic> the CusCFBA complex is the only known RND transporter with a specificity for heavy metals, detoxifying both Cu<jats:sup>+</jats:sup> and Ag<jats:sup>+</jats:sup> ions. In this review, we discuss the known structural information for the CusCFBA proteins, with an emphasis on their assembly, interaction, and the relationship between structure and function.</jats:p>","journal":"Protein Science","year":2015,"id":619797,"datarank":0.637274286307404,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.0,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308715,"name":"Chih‐Chia Su","orcid":"0000-0003-3646-327X","position":1,"is_corresponding":false},{"id":1599704,"name":"Edward W. Yu","orcid":null,"position":2,"is_corresponding":false},{"id":1599703,"name":"Jared A. Delmar","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Heavy metal transport by the <scp>C</scp>us<scp>CFBA</scp> efflux system","abstract":"<jats:title>Abstract</jats:title><jats:p>It is widely accepted that the increased use of antibiotics has resulted in bacteria with developed resistance to such treatments. These organisms are capable of forming multi‐protein structures that bridge both the inner and outer membrane to expel diverse toxic compounds directly from the cell. Proteins of the resistance nodulation cell division (RND) superfamily typically assemble as tripartite efflux pumps, composed of an inner membrane transporter, a periplasmic membrane fusion protein, and an outer membrane factor channel protein. These machines are the most powerful antimicrobial efflux machinery available to bacteria. In <jats:italic>Escherichia coli,</jats:italic> the CusCFBA complex is the only known RND transporter with a specificity for heavy metals, detoxifying both Cu<jats:sup>+</jats:sup> and Ag<jats:sup>+</jats:sup> ions. In this review, we discuss the known structural information for the CusCFBA proteins, with an emphasis on their assembly, interaction, and the relationship between structure and function.</jats:p>","is_dataset_classified":null,"base_score":4.248495242049359,"endowment":4.248495242049359,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26258953","pmcid":"PMC4622206","openalex_id":"https://openalex.org/W1905143287","authors":[],"funders":[{"funder_name":"Office of Extramural Research, National Institutes of Health","grant_id":"R56AI114664","title":null}],"total_grants":1,"fwci":1.1613,"citation_percentile":0.76275825,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":9},{"year":2021,"count":5},{"year":2022,"count":8},{"year":2023,"count":13},{"year":2024,"count":13},{"year":2025,"count":8},{"year":2026,"count":7}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2764","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2764","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fpro.2764","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/pro.2764","host_type":"publisher"},{"url":"https://doi.org/10.1002/pro.2764","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26258953","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4622206","host_type":"repository"}],"fields_of_study":["Trace Elements in Health","Drug Transport and Resistance Mechanisms","Antibiotic Resistance in Bacteria","Drug Resistance, Multiple, Bacterial","Escherichia coli","Escherichia coli Proteins","Membrane Transport Proteins","Metals, Heavy","Models, Molecular"],"mesh_terms":["Escherichia coli","Models, Molecular","Metals, Heavy","Drug Resistance, Multiple, Bacterial","Membrane Transport Proteins","Escherichia coli Proteins"],"keywords":["Efflux","Periplasmic space","Inner membrane","Bacterial outer membrane","Membrane transport protein","Transport protein","Transporter","Escherichia coli","Bacteria","Biology","Multidrug Resistance-Associated Proteins","Membrane protein","Biochemistry","Membrane transport","Cell biology","Chemistry","ATP-binding cassette transporter","Biophysics","Membrane","Genetics","Gene","Heavy metal resistance","Multidrug resistance","Resistance-nodulation-cell Division","Cuscfba Efflux System"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.25376115.v1","title":"Additional file 1 of Early transcriptional changes of heavy metal resistance and multiple efflux genes in Xanthomonas campestris pv. campestris under copper and heavy metal ion stress","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25376115","title":"Additional file 1 of Early transcriptional changes of heavy metal resistance and multiple efflux genes in Xanthomonas campestris pv. campestris under copper and heavy metal ion stress","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25376166","title":"Additional file 2 of Early transcriptional changes of heavy metal resistance and multiple efflux genes in Xanthomonas campestris pv. campestris under copper and heavy metal ion stress","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.25376166.v1","title":"Additional file 2 of Early transcriptional changes of heavy metal resistance and multiple efflux genes in Xanthomonas campestris pv. campestris under copper and heavy metal ion stress","publisher":"figshare","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T08:36:07.910955Z","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":[]}