{"doi":"10.1101/2022.06.09.495520","title":"Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391)","abstract":"Abstract Aggregation of the tau protein into fibrillar cross-β aggregates is a hallmark of Alzheimer’s diseases (AD) and many other neurodegenerative tauopathies. Recently, several core structures of patient-derived tau paired helical filaments (PHFs) have been solved revealing a structural variability that often correlates with a specific tauopathy. To further characterize the dynamics of these fibril cores, to screen for strain-specific small molecules as potential biomarkers and therapeutics, and to develop strain-specific antibodies, recombinant in-vitro models of tau filaments are needed. We recently showed that a 95-residue fragment of tau (from residue 297 to 391), termed dGAE, forms filaments in vitro in the absence of polyanionic co-factors often used for in vitro aggregation of full length tau. Tau(297-391) was identified as the proteolytic resistant core of tau PHFs and overlaps with the structures characterized by cryo-electron microscopy in ex-vivo PHFs, making it a promising model for the study of AD tau filaments in vitro. In the present study, we used solid-state NMR to characterize tau(297-391) filaments and show that such filaments assembled under non-reducing conditions are more dynamic and less ordered than those made in the presence of the reducing agent, DTT. We further report the resonance assignment of tau(297-392)+DTT filaments and compare it to existing core structures of tau.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303518,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9388,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":909804,"name":"Connor Hurt","orcid":null,"position":1,"is_corresponding":false},{"id":909805,"name":"Janet E. Rickard","orcid":null,"position":2,"is_corresponding":false},{"id":909269,"name":"Charles R. Harrington","orcid":"0000-0003-2250-3920","position":3,"is_corresponding":false},{"id":909270,"name":"John M. D. Storey","orcid":"0000-0002-5261-5467","position":4,"is_corresponding":false},{"id":909806,"name":"Claude M. Wischik","orcid":null,"position":5,"is_corresponding":false},{"id":225454,"name":"Louise C. Serpell","orcid":"0000-0001-9335-7751","position":6,"is_corresponding":false},{"id":353565,"name":"Ansgar B. Siemer","orcid":"0000-0003-0901-011X","position":7,"is_corresponding":false},{"id":909268,"name":"Youssra K. Al‐Hilaly","orcid":"0000-0003-2289-4597","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","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":[]}