{"doi":"10.1016/j.str.2025.05.007","title":"Structural insights into functional regulation of the human CPEB3 prion by an amyloid-forming segment","abstract":"The cytoplasmic polyadenylation-element-binding-protein-3 (CPEB3) is a functional prion thought to modulate protein synthesis and enable consolidation of long-term memory in neurons. We report a cryoelectron microscopy (cryo-EM) structure of amyloid fibrils grown in vitro from the first prion-like domain of human CPEB3 (hCPEB3), revealing their ordered 49-residue core, spanning L103 to F151. CPEB3 lacking that segment coalesces into abnormal puncta in cells compared to wild-type CPEB3, localizes away from dormant p-bodies and toward stress granules, and lacks the ability to influence protein synthesis in neurons. Fluorescence-guided cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) applied to neuronal cells expressing CPEB3 reveal CPEB3-GFP signal from lamellae enriched in multivesicular bodies (MVBs), cavernous multilamellar compartments, and bundled filaments, suggesting a state of induced cellular stress. Accordingly, cells expressing wild-type CPEB3 are less viable than those expressing CPEB3 without its amyloid core, suggesting human CPEB3 regulation may be required to overcome the liability associated with its self-assembly in cells.","journal":"Structure","year":2025,"id":541426,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":250200,"name":"M.R. Sawaya","orcid":"0000-0003-0874-9043","position":1,"is_corresponding":false},{"id":250196,"name":"David R. Boyer","orcid":"0000-0002-4487-0230","position":2,"is_corresponding":false},{"id":744989,"name":"Samantha Zink","orcid":"0000-0002-3220-8290","position":3,"is_corresponding":false},{"id":986922,"name":"Susanna Tovmasyan","orcid":null,"position":4,"is_corresponding":false},{"id":986923,"name":"Adrian Saucedo","orcid":null,"position":5,"is_corresponding":false},{"id":409701,"name":"Logan S. Richards","orcid":"0000-0002-1694-1652","position":6,"is_corresponding":false},{"id":805252,"name":"Chih-Te Zee","orcid":"0000-0002-6630-706X","position":7,"is_corresponding":false},{"id":905962,"name":"Jorge Cárdenas","orcid":"0000-0002-4096-2293","position":8,"is_corresponding":false},{"id":429869,"name":"Luana Fioriti","orcid":"0000-0003-2429-8967","position":9,"is_corresponding":false},{"id":355661,"name":"José A. Rodríguez","orcid":"0000-0002-0248-4964","position":10,"is_corresponding":false},{"id":744987,"name":"Maria D. Flores","orcid":"0000-0002-4483-087X","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:52:47.161928Z","pmid":"40480223","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":[]}