| http://purl.uniprot.org/citations/33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33903234 | http://www.w3.org/2000/01/rdf-schema#comment | "Amyloid fibril formation of α-synuclein (αS) is associated with multiple neurodegenerative diseases, including Parkinson's disease (PD). Growing evidence suggests that progression of PD is linked to cell-to-cell propagation of αS fibrils, which leads to seeding of endogenous intrinsically disordered monomer via templated elongation and secondary nucleation. A molecular understanding of the seeding mechanism and driving interactions is crucial to inhibit progression of amyloid formation. Here, using relaxation-based solution NMR experiments designed to probe large complexes, we probe weak interactions of intrinsically disordered acetylated-αS (Ac-αS) monomers with seeding-competent Ac-αS fibrils and seeding-incompetent off-pathway oligomers to identify Ac-αS monomer residues at the binding interface. Under conditions that favor fibril elongation, we determine that the first 11 N-terminal residues on the monomer form a common binding site for both fibrils and off-pathway oligomers. Additionally, the presence of off-pathway oligomers within a fibril seeding environment suppresses seeded amyloid formation, as observed through thioflavin-T fluorescence experiments. This highlights that off-pathway αS oligomers can act as an auto-inhibitor against αS fibril elongation. Based on these data taken together with previous results, we propose a model in which Ac-αS monomer recruitment to the fibril is driven by interactions between the intrinsically disordered monomer N terminus and the intrinsically disordered flanking regions (IDR) on the fibril surface. We suggest that this monomer recruitment may play a role in the elongation of amyloid fibrils and highlight the potential of the IDRs of the fibril as important therapeutic targets against seeded amyloid formation."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2017452118"xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/author | "Wang B."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/author | "Baum J."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/author | "Williams J.K."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/author | "Hoop C.L."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/pages | "e2017452118"xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/title | "NMR unveils an N-terminal interaction interface on acetylated-alpha-synuclein monomers for recruitment to fibrils."xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/33903234 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33903234 |
| http://purl.uniprot.org/citations/33903234 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33903234 |
| http://purl.uniprot.org/uniprot/#_A0A2Z5HU10-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_H6UYS7-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_H6UYS0-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_H6UYS5-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_F6L6N6-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_P37840-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_Q4W5L2-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
| http://purl.uniprot.org/uniprot/#_Q6QBS3-mappedCitation-33903234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33903234 |
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| http://purl.uniprot.org/uniprot/Q4W5L2 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/33903234 |