{"doi":"10.1016/j.molcel.2025.12.022","title":"The ribosome synchronizes folding and assembly to promote oligomeric protein biogenesis","abstract":null,"journal":"Molecular Cell","year":2026,"id":653260,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"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":988227,"name":"Santosh Shivakumaraswamy","orcid":"0000-0002-3852-3582","position":1,"is_corresponding":false},{"id":1704477,"name":"Gabija Jurkeviciute","orcid":null,"position":2,"is_corresponding":false},{"id":1704478,"name":"Jessica Zhiyun He","orcid":null,"position":3,"is_corresponding":false},{"id":1704479,"name":"Josef Auburger","orcid":null,"position":4,"is_corresponding":false},{"id":1704480,"name":"Jaro L. Schmitt","orcid":null,"position":5,"is_corresponding":false},{"id":1704481,"name":"Günter Kramer","orcid":null,"position":6,"is_corresponding":false},{"id":145272,"name":"Bernd Bukau","orcid":null,"position":7,"is_corresponding":false},{"id":1536572,"name":"Radoslav I. Enchev","orcid":null,"position":8,"is_corresponding":false},{"id":988230,"name":"David Balchin","orcid":"0000-0002-5000-0995","position":9,"is_corresponding":false},{"id":988226,"name":"Alžběta Roeselová","orcid":"0000-0002-0175-6462","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The ribosome synchronizes folding and assembly to promote oligomeric protein biogenesis","abstract":"Natural proteins often form intricate multidomain, oligomeric architectures. This presents a prima facie challenge to cellular homeostasis, as topologically complex proteins seldom refold efficiently in vitro . Here, we show that the efficient folding and assembly of the five-domain homotetramer β-galactosidase is obligatorily coupled to its synthesis on the ribosome, and we define the underlying mechanisms. During refolding from a denaturant, maturation of the catalytic domain is frustrated. Assembly outpaces monomer folding, and non-native oligomers accumulate. Efficient de novo folding is characterized by segmental domain folding, shaped by the binding of a nascent amphipathic helix to a cryptic pocket on uL23 on the ribosome surface. Homomer assembly also initiates cotranslationally via recruitment of a full-length subunit to the nascent polypeptide, and the failure to do so results in misassembly. Our results reveal how the ribosome can dictate the timing of folding and assembly to enable efficient biogenesis of a topologically complex protein. • β-gal, a multidomain oligomeric protein, only folds efficiently during translation • On the ribosome, some domains fold segmentally via small units • A groove on the ribosome surface binds and stabilizes a nascent amphipathic helix • β-gal assembly starts during synthesis, avoiding misassembly Large oligomeric proteins constitute a major fraction of proteomes, but are difficult to refold in vitro , raising the question of how cells direct their biogenesis. Roeselová and Shivakumaraswamy et al. show how the ribosome orchestrates efficient cotranslational folding and assembly.","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41558483","pmcid":null,"openalex_id":"https://openalex.org/W7124768052","authors":[],"funders":[{"funder_name":"UK Research and Innovation","grant_id":"EP/X020428/1","title":"FoldingMap: Resolving Protein Biogenesis Pathways"},{"funder_name":"European Commission","grant_id":"101072047","title":"Mechanisms of co-translational assembly of multi-protein complexes"},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Cancer Research UK","grant_id":"","title":null},{"funder_name":"UK Research and Innovation","grant_id":"","title":null},{"funder_name":"European Research Council","grant_id":"","title":null},{"funder_name":"UK Research and Innovation Medical Research Council","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":8,"fwci":8.3553,"citation_percentile":0.9602707,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.molcel.2025.12.022","host_type":"journal"},{"url":"https://doi.org/10.1016/j.molcel.2025.12.022","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1097276525010214?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1097276525010214?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41558483","host_type":"repository"},{"url":"https://doi.org/10.1101/2025.05.27.656346","host_type":""}],"fields_of_study":["RNA and protein synthesis mechanisms","Bacteriophages and microbial interactions","Biochemical and Structural Characterization","0301 basic medicine","03 medical and health sciences","Ribosomes","Protein Folding","beta-Galactosidase","Escherichia coli","Protein Biosynthesis","Models, Molecular","Protein Multimerization","Catalytic Domain","Protein Binding","Protein Refolding"],"mesh_terms":["beta-Galactosidase","Escherichia coli","Models, Molecular","Protein Binding","Ribosomes","Protein Biosynthesis","Protein Folding","Catalytic Domain","Protein Multimerization","Protein Refolding"],"keywords":["Homotetramer","Protein folding","Ribosome","Biogenesis","Folding (DSP implementation)","Protein subunit","Proteostasis","Ribosome biogenesis","Translation (biology)","Cotranslational folding","Protein Assembly","Models, Molecular","Protein Biosynthesis","Catalytic Domain","Escherichia coli","Protein Multimerization","beta-Galactosidase","Ribosomes"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T20:25:53.643016Z","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":[]}