{"doi":"10.1038/nsmb.2108","title":"Mechanism of ubiquitylation by dimeric RING ligase RNF4","abstract":null,"journal":"Nature Structural & Molecular Biology","year":2011,"id":589746,"datarank":7.19060743118629,"base_score":5.236441962829949,"endowment":5.236441962829949,"self_citation_contribution":0.7854662944244925,"citation_network_contribution":6.405141136761798,"self_endowment_contribution":0.7854662944244925,"citer_contribution":6.405141136761798,"corpus_percentile":null,"corpus_rank":null,"citation_count":187,"citer_count":167,"citers_with_citation_signal":147,"citers_with_endowment":147,"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":1508883,"name":"Ellis G Jaffray","orcid":null,"position":1,"is_corresponding":false},{"id":1508885,"name":"Stephen A McMahon","orcid":null,"position":2,"is_corresponding":false},{"id":1508887,"name":"Kenneth A Johnson","orcid":null,"position":3,"is_corresponding":false},{"id":602172,"name":"Iva Navrátilová","orcid":"0000-0003-2762-2056","position":4,"is_corresponding":false},{"id":1508890,"name":"James H Naismith","orcid":null,"position":5,"is_corresponding":false},{"id":1508891,"name":"Ronald T Hay","orcid":null,"position":6,"is_corresponding":false},{"id":1508882,"name":"Anna Plechanovová","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mechanism of ubiquitylation by dimeric RING ligase RNF4","abstract":"Mammalian RNF4 is a dimeric RING ubiquitin E3 ligase that ubiquitylates poly-SUMOylated proteins. We found that RNF4 bound ubiquitin-charged UbcH5a tightly but free UbcH5a weakly. To provide insight into the mechanism of RING-mediated ubiquitylation, we docked the UbcH5~ubiquitin thioester onto the RNF4 RING structure. This revealed that with E2 bound to one monomer of RNF4, the thioester-linked ubiquitin could reach across the dimer to engage the other monomer. In this model, the 'Ile44 hydrophobic patch' of ubiquitin is predicted to engage a conserved tyrosine located at the dimer interface of the RING, and mutation of these residues blocked ubiquitylation activity. Thus, dimeric RING ligases are not simply inert scaffolds that bring substrate and E2-loaded ubiquitin into close proximity. Instead, they facilitate ubiquitin transfer by preferentially binding the E2~ubiquitin thioester across the dimer and activating the thioester bond for catalysis.","is_dataset_classified":null,"base_score":5.236441962829949,"endowment":5.236441962829949,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21857666","pmcid":"PMC3326525","openalex_id":"https://openalex.org/W1979019144","authors":[],"funders":[{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BBS/B/14426","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Cancer Research UK","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Cancer Research UK","grant_id":"","title":null}],"total_grants":6,"fwci":6.0825,"citation_percentile":0.9739406,"influential_citations":0,"citation_trend":[{"year":2012,"count":17},{"year":2013,"count":20},{"year":2014,"count":11},{"year":2015,"count":9},{"year":2016,"count":16},{"year":2017,"count":12},{"year":2018,"count":7},{"year":2019,"count":11},{"year":2020,"count":15},{"year":2021,"count":17},{"year":2022,"count":12},{"year":2023,"count":11},{"year":2024,"count":8},{"year":2025,"count":11},{"year":2026,"count":8}],"oa_status":"green","license":"Springer TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3326525","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3326525","host_type":"repository"},{"url":"http://www.nature.com/articles/nsmb.2108.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/nsmb.2108","host_type":"publisher"},{"url":"https://doi.org/10.1038/nsmb.2108","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21857666","host_type":"repository"},{"url":"https://discovery.dundee.ac.uk/en/publications/d9e692b5-d700-414a-9a6f-f24c668353e2","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc3326525?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.1038/nsmb.2108","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/nsmb.2108","host_type":""}],"fields_of_study":["Ubiquitin and proteasome pathways","Cancer-related Molecular Pathways","Protein Degradation and Inhibitors","0301 basic medicine","03 medical and health sciences","0303 health sciences","Animals","Binding, Competitive","Catalytic Domain","Dimerization","Models, Molecular","Nuclear Proteins","Protein Structure, Tertiary","RING Finger Domains","Rats","Recombinant Fusion Proteins","Transcription Factors","Ubiquitin-Conjugating Enzymes","Ubiquitin-Protein Ligases","Ubiquitination"],"mesh_terms":["Animals","Binding, Competitive","Models, Molecular","Nuclear Proteins","Recombinant Fusion Proteins","Transcription Factors","Protein Structure, Tertiary","Dimerization","Catalytic Domain","Ubiquitin-Conjugating Enzymes","Ubiquitin-Protein Ligases","Rats","RING Finger Domains","Ubiquitination"],"keywords":["Ubiquitin ligase","Thioester","Ubiquitin","RNF4","Chemistry","Ubiquitin-Protein Ligases","Dimer","Ubiquitin-conjugating enzyme","DNA ligase","Stereochemistry","Biophysics","Biochemistry","DNA","Transcription factor","Zinc finger","Biology","Enzyme","Models, Molecular","DIMERIZATION","570","SUMO-BINDING MOTIF","PROTEINS","Recombinant Fusion Proteins","HETERODIMER","Binding, Competitive","E3 UBIQUITIN LIGASES","E2","Catalytic Domain","Animals","CRYSTAL-STRUCTURE","COMPLEX","IDENTIFICATION","RECOGNITION","Ubiquitination","Nuclear Proteins","Protein Structure, Tertiary","Rats","Ubiquitin-Conjugating Enzymes","RING Finger Domains","Transcription Factors"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T05:56:38.937129Z","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":[]}