{"doi":"10.1101/2020.12.31.424989","title":"Distinct cryo-EM Structure of α-synuclein Filaments derived by Tau","abstract":"Abstract Recent structural studies of ex vivo amyloid filaments extracted from human patients demonstrated that the ex vivo filaments associated with different disease phenotypes adopt diverse molecular conformations distinct from those in vitro amyloid filaments. A very recent cryo-EM structural study also revealed that ex vivo α-synuclein filaments extracted from multiple system atrophy (MSA) patients adopt quite distinct molecular structures from those of in vitro α-synuclein filaments, suggesting the presence of co-factors for α-synuclein aggregation in vivo. Here, we report structural characterizations of α-synuclein filaments derived by a potential co-factor, tau, using cryo-EM and solid-state NMR. Our cryo-EM structure of the tau-promoted α-synuclein filament at 4.0 Å resolution is somewhat similar to one of the polymorphs of in vitro α-synuclein filaments. However, the N- and C-terminal regions of the tau-promoted α-synuclein filament have different molecular conformations. Our structural studies highlight the conformational plasticity of α-synuclein filaments, requiring additional structural investigation of not only more ex vivo α-synuclein filaments, but also in vitro α-synuclein filaments formed in the presence of diverse co-factors to better understand molecular basis of diverse molecular conformations of α-synuclein filaments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214699,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9422,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":441250,"name":"Anvesh K. R. Dasari","orcid":"0000-0001-7248-1876","position":1,"is_corresponding":false},{"id":622006,"name":"Urmi Sengupta","orcid":"0000-0002-8034-6241","position":2,"is_corresponding":false},{"id":494331,"name":"Dianne W. Taylor","orcid":"0000-0002-2033-4978","position":3,"is_corresponding":false},{"id":494330,"name":"Nadia Daneshparvar","orcid":"0000-0002-5661-1228","position":4,"is_corresponding":false},{"id":494333,"name":"Fatemeh Abbasi Yeganeh","orcid":"0000-0001-5540-5927","position":5,"is_corresponding":false},{"id":559409,"name":"Lucas Dillard","orcid":"0000-0003-4325-8055","position":6,"is_corresponding":false},{"id":442492,"name":"Brian Michael","orcid":null,"position":7,"is_corresponding":false},{"id":340244,"name":"Robert G. Griffin","orcid":"0000-0003-1589-832X","position":8,"is_corresponding":false},{"id":227365,"name":"Mario J. Borgnia","orcid":"0000-0001-9159-1413","position":9,"is_corresponding":false},{"id":236490,"name":"Rakez Kayed","orcid":"0000-0001-6216-8640","position":10,"is_corresponding":false},{"id":494334,"name":"Kenneth A. Taylor","orcid":"0000-0001-9594-8360","position":11,"is_corresponding":false},{"id":441252,"name":"Kwang Hun Lim","orcid":"0000-0002-0971-200X","position":12,"is_corresponding":false},{"id":579610,"name":"Alimohammad Hojjatian","orcid":"0000-0002-6023-5923","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","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":[]}