{"doi":"10.1101/2024.09.09.612142","title":"Intact cells selectively amplify and structurally remodel amyloid fibrils","abstract":"Abstract Amyloid forms of α-synuclein adopt different conformations depending on environmental conditions. Although advances in structural biology have accelerated fibril characterization, it remains unclear which conformations predominate in biological settings because current approaches typically require fibrils to be isolated from their native environments. In addition, these approaches provide limited information about flanking flexible regions. Here, using a defined polymorphic seed population and quantitative in-cell NMR, we show that propagation in intact cellular environments—but not in vitro buffer or crowded cellular lysates—reshapes the conformational ensemble of α-synuclein fibrils. In vitro and in cellular lysates, both amyloid-core structure and the conformational preferences of flanking intrinsically disordered regions of the seed are faithfully propagated. In contrast, propagation inside intact cells selectively amplifies the amyloid-core conformer that is minor in vitro, increases its molecular order, and remodels conformational preferences in the flanking disordered region. These results demonstrate that cellular organization plays a decisive role in determining amyloid structure and that biologically relevant conformations cannot be inferred from purified or lysate systems alone.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485693,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1170179,"name":"Dominique Lagasca","orcid":"0000-0003-4404-4366","position":1,"is_corresponding":false},{"id":1009977,"name":"Rania Dumarieh","orcid":"0000-0002-4462-7134","position":2,"is_corresponding":false},{"id":417482,"name":"Yiling Xiao","orcid":"0000-0002-4548-4833","position":3,"is_corresponding":false},{"id":1170180,"name":"Sakshi Krishna","orcid":"0000-0002-4223-0379","position":4,"is_corresponding":false},{"id":1268559,"name":"Yang Li","orcid":"0000-0001-9601-4885","position":5,"is_corresponding":false},{"id":417483,"name":"Kendra K. Frederick","orcid":"0000-0002-1656-5167","position":6,"is_corresponding":false},{"id":1329202,"name":"Shoyab Ansari","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":"39314304","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":[]}