{"doi":"10.1126/science.1131167","title":"C-Terminal Signal Sequence Promotes Virulence Factor Secretion in\n                    <i>Mycobacterium tuberculosis</i>","abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis</jats:italic>\n                    uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from\n                    <jats:italic>M. tuberculosis</jats:italic>\n                    cells, demonstrating that this ESX-1 signal is portable.\n                  </jats:p>","journal":"Science","year":2006,"id":633381,"datarank":0.8182981673036553,"base_score":5.455321115357702,"endowment":5.455321115357702,"self_citation_contribution":0.8182981673036553,"citation_network_contribution":0.0,"self_endowment_contribution":0.8182981673036553,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":233,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":15461,"name":"Sarah A. Stanley","orcid":"0000-0002-0253-2663","position":1,"is_corresponding":false},{"id":416106,"name":"Matthew M. Champion","orcid":"0000-0001-5927-5277","position":2,"is_corresponding":false},{"id":569798,"name":"Eric J. Brown","orcid":"0000-0003-2125-6286","position":3,"is_corresponding":false},{"id":251792,"name":"Jeffery S. Cox","orcid":"0000-0002-5061-6618","position":4,"is_corresponding":false},{"id":1642105,"name":"Patricia A. DiGiuseppe Champion","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"C-Terminal Signal Sequence Promotes Virulence Factor Secretion in\n                    <i>Mycobacterium tuberculosis</i>","abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis</jats:italic>\n                    uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from\n                    <jats:italic>M. tuberculosis</jats:italic>\n                    cells, demonstrating that this ESX-1 signal is portable.\n                  </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16973880","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"PHS HHS","grant_id":"A105155","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI51667","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI63302","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":14,"citation_trend":[],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.1131167","host_type":"publisher"}],"fields_of_study":["Biology","Medicine"],"mesh_terms":["Mycobacterium tuberculosis","Protein Sorting Signals","Bacterial Proteins","Membrane Proteins","Recombinant Fusion Proteins","Ubiquitin","Virulence Factors","Antigens, Bacterial","Two-Hybrid System Techniques","Amino Acid Sequence","Protein Structure, Tertiary","Protein Binding","Protein Transport","Dimerization","Mutation","Models, Biological","Molecular Sequence Data"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T11:57:50.344118Z","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":[]}