{"doi":"10.1111/mmi.12857","title":"A two‐component, multimeric endolysin encoded by a single gene","abstract":"<jats:title>Summary</jats:title><jats:p>Bacteriophage endolysins are bacterial cell wall degrading enzymes whose potential to fight bacterial infections has been intensively studied. Endolysins from Gram‐positive systems are typically described as monomeric and as having a modular structure consisting of one or two <jats:styled-content style=\"fixed-case\">N</jats:styled-content>‐terminal catalytic domains (<jats:styled-content style=\"fixed-case\">CD</jats:styled-content>s) linked to a <jats:styled-content style=\"fixed-case\">C</jats:styled-content>‐terminal region responsible for cell wall binding (<jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>). We show here that expression of the endolysin gene <jats:italic>lys170</jats:italic> of the enterococcal phage <jats:styled-content style=\"fixed-case\">F</jats:styled-content>170/08 results in two products, the expected full length endolysin (<jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170<jats:styled-content style=\"fixed-case\">FL</jats:styled-content>) and a <jats:styled-content style=\"fixed-case\">C</jats:styled-content>‐terminal fragment corresponding to the <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content> domain (<jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170). The latter is produced from an in‐frame, alternative translation start site. Both polypeptides interact to form the fully active endolysin. Biochemical data strongly support a model where <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170 is made of one monomer of <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170<jats:styled-content style=\"fixed-case\">FL</jats:styled-content> associated with up to three <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170 subunits, which are responsible for efficient endolysin binding to its substrate. Bioinformatics analysis indicates that similar secondary translation start signals may be used to produce and add independent <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170‐like subunits to different enzymatic specificities. The particular configuration of endolysin <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170 uncovers a new mode of increasing the number of <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content> motifs associated to <jats:styled-content style=\"fixed-case\">CD</jats:styled-content> modules, as an alternative to the tandem repetition typically found in monomeric cell wall hydrolases.</jats:p>","journal":"Molecular Microbiology","year":2015,"id":677115,"datarank":0.5289540786924243,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.0,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"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":1769181,"name":"Christophe Velours","orcid":null,"position":1,"is_corresponding":false},{"id":1769184,"name":"Clara Leandro","orcid":null,"position":2,"is_corresponding":false},{"id":67296,"name":"Miguel Garcia","orcid":null,"position":3,"is_corresponding":false},{"id":355452,"name":"Madalena Pimentel","orcid":"0000-0002-4598-1290","position":4,"is_corresponding":false},{"id":1769187,"name":"Carlos São‐José","orcid":null,"position":5,"is_corresponding":false},{"id":1769178,"name":"Daniela Proença","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A two‐component, multimeric endolysin encoded by a single gene","abstract":"<jats:title>Summary</jats:title><jats:p>Bacteriophage endolysins are bacterial cell wall degrading enzymes whose potential to fight bacterial infections has been intensively studied. Endolysins from Gram‐positive systems are typically described as monomeric and as having a modular structure consisting of one or two <jats:styled-content style=\"fixed-case\">N</jats:styled-content>‐terminal catalytic domains (<jats:styled-content style=\"fixed-case\">CD</jats:styled-content>s) linked to a <jats:styled-content style=\"fixed-case\">C</jats:styled-content>‐terminal region responsible for cell wall binding (<jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>). We show here that expression of the endolysin gene <jats:italic>lys170</jats:italic> of the enterococcal phage <jats:styled-content style=\"fixed-case\">F</jats:styled-content>170/08 results in two products, the expected full length endolysin (<jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170<jats:styled-content style=\"fixed-case\">FL</jats:styled-content>) and a <jats:styled-content style=\"fixed-case\">C</jats:styled-content>‐terminal fragment corresponding to the <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content> domain (<jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170). The latter is produced from an in‐frame, alternative translation start site. Both polypeptides interact to form the fully active endolysin. Biochemical data strongly support a model where <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170 is made of one monomer of <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170<jats:styled-content style=\"fixed-case\">FL</jats:styled-content> associated with up to three <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170 subunits, which are responsible for efficient endolysin binding to its substrate. Bioinformatics analysis indicates that similar secondary translation start signals may be used to produce and add independent <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content>170‐like subunits to different enzymatic specificities. The particular configuration of endolysin <jats:styled-content style=\"fixed-case\">L</jats:styled-content>ys170 uncovers a new mode of increasing the number of <jats:styled-content style=\"fixed-case\">CWB</jats:styled-content> motifs associated to <jats:styled-content style=\"fixed-case\">CD</jats:styled-content> modules, as an alternative to the tandem repetition typically found in monomeric cell wall hydrolases.</jats:p>","is_dataset_classified":null,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25388025","pmcid":null,"openalex_id":"https://openalex.org/W2131476067","authors":[],"funders":[],"total_grants":0,"fwci":1.9829,"citation_percentile":0.85729309,"influential_citations":0,"citation_trend":[{"year":2015,"count":3},{"year":2016,"count":3},{"year":2017,"count":1},{"year":2018,"count":5},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":2},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.12857","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.12857","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fmmi.12857","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/mmi.12857","host_type":"publisher"},{"url":"https://doi.org/10.1111/mmi.12857","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25388025","host_type":"repository"},{"url":"https://hal.science/hal-02400295","host_type":"repository"},{"url":"http://hdl.handle.net/10400.26/18714","host_type":"repository"}],"fields_of_study":["Bacteriophages and microbial interactions","Genomics and Phylogenetic Studies","Legume Nitrogen Fixing Symbiosis","Amino Acid Sequence","Bacteriophages","Binding Sites","Cell Wall","Computational Biology","Endopeptidases","Enterococcus","Escherichia coli","Multiprotein Complexes","Protein Binding","Protein Multimerization","Protein Structure, Tertiary","Protein Subunits","Sequence Homology, Amino Acid"],"mesh_terms":["Amino Acid Sequence","Bacteriophages","Binding Sites","Cell Wall","Escherichia coli","Endopeptidases","Protein Binding","Enterococcus","Sequence Homology, Amino Acid","Protein Structure, Tertiary","Computational Biology","Protein Subunits","Multiprotein Complexes","Protein Multimerization"],"keywords":["Lysin","Biology","Bacteriophage","Bacterial cell structure","Protein subunit","Biochemistry","Enzyme","Gene","Bacteria","Genetics","Escherichia coli"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T03:40:24.482457Z","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":[]}