{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Grabarczyk DB"],"funding":["Austrian Science Fund FWF"],"pagination":["909-914"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618180"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["389(6763)"],"pubmed_abstract":["Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48-specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is co"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control."],"pmcid":["PMC7618180"],"funding_grant_id":["DOC 112","ESP 218"],"pubmed_authors":["Zavodszky E","Kurzbauer R","Song HK","Deszcz L","Grabarczyk DB","Shulkina A","Lee J","Hegde RS","Bell LE","Versteeg GA","Murphy P","Ehrmann JF","Yang WS","Neuhold J","Schleiffer A","Shin JS","Clausen T","Meinhart A"],"additional_accession":[]},"is_claimable":false,"name":"Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.","description":"Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48-specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is co","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-03T22:56:55.896Z","creation":"2026-05-02T03:12:01.585Z"},"accession":"S-EPMC7618180","cross_references":{"pubmed":["40875847"],"doi":["10.1126/science.adv9309"]}}