{"doi":"10.1101/2024.07.01.601365","title":"Structure of a novel α-synuclein filament fold from multiple system atrophy","abstract":"Abstract Multiple system atrophy (MSA) is a synucleinopathy, a group of related diseases characterized by the accumulation of α-synuclein aggregates in the brain. In MSA, these aggregates form glial cytoplasmic inclusions, which contain abundant cross-β amyloid filaments. Structures of α-synuclein filaments isolated from MSA patient tissue were determined by cryo–electron microscopy (cryo-EM), revealing three discrete folds that are distinct from α-synuclein filaments associated with other synucleinopathies. Here, we use cryo-EM classification methods to characterize filaments from one individual with MSA and identify a novel, low-populated MSA filament fold (designated Type I 2 ) in addition to a predominant class comprising MSA Type II 2 . The 3.3-Å resolution structure of the Type I 2 filament reveals a fold consisting of two asymmetric protofilaments. One is identical to a previously solved Type I protofilament, while the second adopts a novel fold that is chimeric between two previously reported Type I and II protofilaments. These results further define disease-specific folds of α-synuclein filaments that develop in MSA and have implications for the design of therapeutic and diagnostic molecules that target disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491317,"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":0.9421,"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":1336928,"name":"Francisco Candido","orcid":null,"position":1,"is_corresponding":false},{"id":227715,"name":"Eric Tse","orcid":"0000-0002-2082-9006","position":2,"is_corresponding":false},{"id":108160,"name":"Arthur A. Melo","orcid":"0000-0002-9345-1462","position":3,"is_corresponding":false},{"id":5842,"name":"Stanley B. Prusiner","orcid":"0000-0003-1955-5498","position":4,"is_corresponding":false},{"id":347215,"name":"Daniel A. Mordes","orcid":"0000-0002-4805-7394","position":5,"is_corresponding":false},{"id":565763,"name":"Daniel R. Southworth","orcid":"0000-0001-7108-9389","position":6,"is_corresponding":false},{"id":5843,"name":"Nick A. Paras","orcid":"0000-0001-5742-4056","position":7,"is_corresponding":false},{"id":108129,"name":"Gregory E. Merz","orcid":"0000-0003-0842-4935","position":8,"is_corresponding":false},{"id":510384,"name":"N. Yan","orcid":"0000-0003-4978-550X","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:08:41.211111Z","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":[]}