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http://purl.uniprot.org/citations/17222866http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17222866http://www.w3.org/2000/01/rdf-schema#comment"To investigate the alpha-synuclein protein and its role in Parkinson's disease, we screened a library of random point mutants both in vitro and in yeast to find variants in an unbiased way that could help us understand the sequence-phenotype relationship. We developed a rapid purification method that allowed us to screen 59 synuclein mutants in vitro and discovered two double-point mutants that fibrillized slowly relative to wild-type, A30P, and A53T alpha-synucleins. The yeast toxicity of all of these proteins was measured, and we found no correlation with fibrillization rate, suggesting that fibrillization is not necessary for synuclein-induced yeast toxicity. We found that beta-synuclein was of intermediate toxicity to yeast, and gamma-synuclein was non-toxic. Co-expression of Parkinson's disease-related genes DJ-1, parkin, Pink1, UCH-L1, or synphilin, with synuclein, did not affect synuclein toxicity. A second screen, of several thousand library clones in yeast, identified 25 non-toxic alpha-synuclein sequence variants. Most of these contained a mutation to either proline or glutamic acid that caused a defect in membrane binding. We hypothesize that yeast toxicity is caused by synuclein binding directly to membranes at levels sufficient to non-specifically disrupt homeostasis."xsd:string
http://purl.uniprot.org/citations/17222866http://purl.org/dc/terms/identifier"doi:10.1016/j.jmb.2006.12.044"xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/author"Lansbury P.T. Jr."xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/author"Volles M.J."xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/name"J Mol Biol"xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/pages"1510-1522"xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/title"Relationships between the sequence of alpha-synuclein and its membrane affinity, fibrillization propensity, and yeast toxicity."xsd:string
http://purl.uniprot.org/citations/17222866http://purl.uniprot.org/core/volume"366"xsd:string
http://purl.uniprot.org/citations/17222866http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17222866
http://purl.uniprot.org/citations/17222866http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17222866
http://purl.uniprot.org/uniprot/O55042#attribution-4CAE0B16C0FE6F09D3BC2A11569899A8http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/17222866
http://purl.uniprot.org/uniprot/P37840#attribution-4CAE0B16C0FE6F09D3BC2A11569899A8http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/17222866
http://purl.uniprot.org/uniprot/Q16143#attribution-4CAE0B16C0FE6F09D3BC2A11569899A8http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/17222866
http://purl.uniprot.org/uniprot/O76070#attribution-4CAE0B16C0FE6F09D3BC2A11569899A8http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/17222866
http://purl.uniprot.org/uniprot/#_O55042-mappedCitation-17222866http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17222866
http://purl.uniprot.org/uniprot/O55042http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/17222866