{"doi":"10.1073/pnas.250277297","title":"A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: Implications for filovirus budding","abstract":"<jats:p>\n                    VP40, the putative matrix protein of both Ebola and Marburg\n viruses, possesses a conserved proline-rich motif (PY motif) at its N\n terminus. We demonstrate that the VP40 protein can mediate its own\n release from mammalian cells, and that the PY motif is important for\n this self-exocytosis (budding) function. In addition, we used\n Western-ligand blotting to demonstrate that the PY motif of VP40 can\n mediate interactions with specific cellular proteins that have type I\n WW-domains, including the mammalian ubiquitin ligase, Nedd4. Single\n point mutations that disrupted the PY motif of VP40 abolished the\n PY/WW-domain interactions. Significantly, the full-length VP40\n protein was shown to interact both physically and functionally with\n full-length Rsp5, a ubiquitin ligase of yeast and homolog of Nedd4. The\n VP40 protein was multiubiquitinated by Rsp5 in a PY-dependent manner in\n an\n                    <jats:italic>in vitro</jats:italic>\n                    ubiquitination assay. These data demonstrate\n that the VP40 protein of Ebola virus possesses a PY motif that is\n functionally similar to those described previously for Gag and M\n proteins of specific retroviruses and rhabdoviruses, respectively.\n Last, these studies imply that VP40 likely plays an important role in\n filovirus budding, and that budding of retroviruses, rhabdoviruses, and\n filoviruses may proceed via analogous mechanisms.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":592109,"datarank":13.85816116156356,"base_score":6.104793232414985,"endowment":6.104793232414985,"self_citation_contribution":0.9157189848622479,"citation_network_contribution":12.942442176701311,"self_endowment_contribution":0.9157189848622479,"citer_contribution":12.942442176701311,"corpus_percentile":null,"corpus_rank":null,"citation_count":447,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"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":1515105,"name":"Melissa E. Brown","orcid":null,"position":1,"is_corresponding":false},{"id":764487,"name":"Guangli Wang","orcid":"0000-0003-2161-264X","position":2,"is_corresponding":false},{"id":1515106,"name":"Jon Huibregtse","orcid":null,"position":3,"is_corresponding":false},{"id":1515107,"name":"Felicia P. Hayes","orcid":null,"position":4,"is_corresponding":false},{"id":396775,"name":"Ronald N. Harty","orcid":"0000-0001-6596-0414","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: Implications for filovirus budding","abstract":"<jats:p>\n                    VP40, the putative matrix protein of both Ebola and Marburg\n viruses, possesses a conserved proline-rich motif (PY motif) at its N\n terminus. We demonstrate that the VP40 protein can mediate its own\n release from mammalian cells, and that the PY motif is important for\n this self-exocytosis (budding) function. In addition, we used\n Western-ligand blotting to demonstrate that the PY motif of VP40 can\n mediate interactions with specific cellular proteins that have type I\n WW-domains, including the mammalian ubiquitin ligase, Nedd4. Single\n point mutations that disrupted the PY motif of VP40 abolished the\n PY/WW-domain interactions. Significantly, the full-length VP40\n protein was shown to interact both physically and functionally with\n full-length Rsp5, a ubiquitin ligase of yeast and homolog of Nedd4. The\n VP40 protein was multiubiquitinated by Rsp5 in a PY-dependent manner in\n an\n                    <jats:italic>in vitro</jats:italic>\n                    ubiquitination assay. These data demonstrate\n that the VP40 protein of Ebola virus possesses a PY motif that is\n functionally similar to those described previously for Gag and M\n proteins of specific retroviruses and rhabdoviruses, respectively.\n Last, these studies imply that VP40 likely plays an important role in\n filovirus budding, and that budding of retroviruses, rhabdoviruses, and\n filoviruses may proceed via analogous mechanisms.\n                  </jats:p>","is_dataset_classified":null,"base_score":6.104793232414985,"endowment":6.104793232414985,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11095724","pmcid":"PMC17668","openalex_id":"https://openalex.org/W2008316672","authors":[],"funders":[],"total_grants":0,"fwci":14.1296,"citation_percentile":0.99432664,"influential_citations":0,"citation_trend":[{"year":2012,"count":18},{"year":2013,"count":20},{"year":2014,"count":16},{"year":2015,"count":22},{"year":2016,"count":17},{"year":2017,"count":19},{"year":2018,"count":19},{"year":2019,"count":13},{"year":2020,"count":16},{"year":2021,"count":22},{"year":2022,"count":12},{"year":2023,"count":11},{"year":2024,"count":9},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.250277297","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.250277297","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11095724","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC17668","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/17668","host_type":"repository"}],"fields_of_study":["Viral Infections and Outbreaks Research","Viral Infections and Vectors","Hepatitis B Virus Studies"],"mesh_terms":["Nedd4 Ubiquitin Protein Ligases","Amino Acid Sequence","Animals","Calcium-Binding Proteins","Cell Line","Ligases","Molecular Sequence Data","Nucleoproteins","Protein Binding","Viral Core Proteins","Virus Replication","Amino Acid Motifs","Ebolavirus","Ubiquitin-Protein Ligases","Endosomal Sorting Complexes Required for Transport"],"keywords":["VP40","Ubiquitin ligase","NEDD4","Biology","Ubiquitin","Ebola virus","Cell biology","WW domain","Filoviridae","Ebolavirus","Virology","Virus","Genetics","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T12:14:28.676955Z","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":[]}