{"doi":"10.1016/j.jmb.2025.169056","title":"Mechanistic Insights into Protein Biogenesis and Maturation on the Ribosome","abstract":"• Diverse protein biogenesis machineries converge at the ribosome to assist in the maturation of the nascent proteome. • The ribosome and molecular chaperones cooperate to regulate nascent protein folding. • The synthesis of endomembrane proteins is coupled to their localization and folding at the endoplasmic reticulum membrane. • Cotranslational protein biogenesis pathways are regulated by a combination of competition, allosteric, and timing mechanisms. • NAC acts as an assembly hub at the ribosome and rectifies the sorting of nascent proteins into the correct maturation pathway. The ribosome is a major cellular machine that converts genetic information into biological function. Emerging data show that the ribosome is not only a protein synthesis machine, but also participates in the maturation of the nascent protein into properly folded and active molecules. The ribosome surface near the opening of the polypeptide exit tunnel can interact directly with the newly synthesized proteins and, more importantly, provides a platform where numerous protein biogenesis factors assemble, gain access to the nascent chain, and direct them into diverse biogenesis pathways. In this article, we review the current understanding of cotranslational protein maturation pathways, with an emphasis on systems in which biochemical studies provided a high-resolution molecular understanding and yielded generalizable mechanistic principles.","journal":"Journal of Molecular Biology","year":2025,"id":531162,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344908,"name":"Jae Ho Lee","orcid":"0000-0002-8663-3209","position":1,"is_corresponding":false},{"id":344909,"name":"Shu‐ou Shan","orcid":"0000-0002-6526-1733","position":2,"is_corresponding":false},{"id":714171,"name":"Alfred M. Lentzsch","orcid":"0000-0002-8150-0511","position":0,"is_corresponding":true}],"reference_count":250,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"40024436","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":[]}