{"doi":"10.1371/journal.pone.0049750","title":"Site-Specific Perturbations of Alpha-Synuclein Fibril Structure by the Parkinson's Disease Associated Mutations A53T and E46K","abstract":null,"journal":"PLoS ONE","year":2013,"id":641266,"datarank":0.6261580904843456,"base_score":4.174387269895637,"endowment":4.174387269895637,"self_citation_contribution":0.6261580904843456,"citation_network_contribution":0.0,"self_endowment_contribution":0.6261580904843456,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1667143,"name":"Gemma Comellas","orcid":null,"position":1,"is_corresponding":false},{"id":1667144,"name":"Shin W. Lee","orcid":null,"position":2,"is_corresponding":false},{"id":1667145,"name":"Lars K. Rikardsen","orcid":null,"position":3,"is_corresponding":false},{"id":510922,"name":"Wendy S. Woods","orcid":null,"position":4,"is_corresponding":false},{"id":550057,"name":"Julia M. George","orcid":"0000-0001-6194-6914","position":5,"is_corresponding":false},{"id":526696,"name":"Chad M. Rienstra","orcid":"0000-0002-9912-5596","position":6,"is_corresponding":false},{"id":1667142,"name":"Luisel R. Lemkau","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Site-Specific Perturbations of Alpha-Synuclein Fibril Structure by the Parkinson's Disease Associated Mutations A53T and E46K","abstract":"Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils.","is_dataset_classified":null,"base_score":4.174387269895637,"endowment":4.174387269895637,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23505409","pmcid":"PMC3591419","openalex_id":"https://openalex.org/W1989992777","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM073770","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM073770","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"S10 RR025037","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"S10RR025037-01","title":null},{"funder_name":"National Institutes of Health","grant_id":"1S10RR025037-01","title":"High-Field, Wide-Bore Solid-State NMR Spectrometer for Membrane Protein Structure"},{"funder_name":"National Institutes of Health","grant_id":"3R01GM073770-03S1","title":"Structures of Protein Aggregates by Solid-State 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NMR Techniques and Applications","Parkinson's Disease Mechanisms and Treatments","Advanced Neuroimaging Techniques and Applications","0301 basic medicine","0303 health sciences","03 medical and health sciences","Amino Acid Sequence","Humans","Lewy Bodies","Molecular Sequence Data","Mutant Proteins","Mutation","Nuclear Magnetic Resonance, Biomolecular","Parkinson Disease","Protein Structure, Secondary","alpha-Synuclein"],"mesh_terms":["Amino Acid Sequence","Humans","Molecular Sequence Data","Mutation","Parkinson Disease","Lewy Bodies","Protein Structure, Secondary","Nuclear Magnetic Resonance, Biomolecular","Mutant Proteins","alpha-Synuclein"],"keywords":["Fibril","Alpha-synuclein","Substantia nigra","Mutant","Mutation","Chemistry","Biophysics","Biology","Parkinson's disease","Biochemistry","Dopaminergic","Neuroscience","Pathology","Medicine","Dopamine","Disease","Gene","Protein Structure","Secondary","Nuclear Magnetic Resonance","Science","Q","Molecular Sequence Data","R","Parkinson Disease","Protein Structure, Secondary","Humans","Lewy Bodies","Mutant Proteins","Amino Acid Sequence","Nuclear Magnetic Resonance, Biomolecular","Biomolecular","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T16:56:11.165346Z","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":[]}