The chaperone activity of a-synuclein: Utilizing deletion mutants to map its interaction with target proteins

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dc.contributor.authorRekas, Aen_AU
dc.contributor.authorAhn, KJen_AU
dc.contributor.authorKim, Jen_AU
dc.contributor.authorCarver, JAen_AU
dc.date.accessioned2012-06-20T02:59:43Zen_AU
dc.date.available2012-06-20T02:59:43Zen_AU
dc.date.issued2012-03-01en_AU
dc.date.statistics2012-06-20en_AU
dc.description.abstracta-Synuclein is the principal component of the Lewy body deposits that are characteristic of Parkinson's disease. In vivo, and under physiological conditions in vitro, a-synuclein aggregates to form amyloid fibrils, a process that is likely to be associated with the development of Parkinson's disease. a-Synuclein also possesses chaperone activity to prevent the precipitation of amorphously aggregating target proteins, as demonstrated in vitro. a-Synuclein is an intrinsically disordered (i.e., unstructured) protein of 140 amino acids in length, and therefore studies on its fragments can be correlated directly to the functional role of these regions in the intact protein. In this study, the fragment containing residues 61140 [a-syn(61140)] was observed to be highly amyloidogenic and was as effective a chaperone in vitro as the full-length protein, while the N- and C-terminal fragments a-syn(160) and a-syn(96140) had no intrinsic chaperone activity. Interestingly, full-length fibrillar a-synuclein had greater chaperone activity than nonfibrillar a-synuclein. It is concluded that the amyloidogenic NAC region (residues 6195) contains the chaperone-binding site which is optimized for target protein binding as a result of its beta-sheet formation and/or ordered aggregation by a-synuclein. On the other hand, the first 60 residues of a-synuclein modulate the protein's chaperone-active site, while at the same time protecting a-synuclein from fibrillation. On its own, however, this fragment [a-syn(160)] had a tendency to aggregate amorphously. As a result of this study, the functional roles of the various regions of a-synuclein in its chaperone activity have been delineated. Proteins 2012; (c) 2011 Wiley Periodicals, Inc.en_AU
dc.identifier.citationRekas, A., Ahn, K. J., Kim, J., & Carver, J. A. (2012). The chaperone activity of a-synuclein: utilizing deletion mutants to map its interaction with target proteins. Proteins: Structure, Function, and Bioinformatics, 80(5), 1316-1325. doi:10.1002/prot.24028en_AU
dc.identifier.govdoc4302en_AU
dc.identifier.issn0887-3585en_AU
dc.identifier.issue5en_AU
dc.identifier.journaltitleProteins: Structure, Function, and Bioinformaticsen_AU
dc.identifier.pagination1316-1325en_AU
dc.identifier.urihttp://dx.doi.org/10.1002/prot.24028en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/4346en_AU
dc.identifier.volume80en_AU
dc.language.isoenen_AU
dc.publisherWiley-Blackwellen_AU
dc.subjectMutantsen_AU
dc.subjectLight scatteringen_AU
dc.subjectAgglomerationen_AU
dc.subjectCrystalline lensen_AU
dc.subjectPhysiologyen_AU
dc.subjectHeat-shock proteinsen_AU
dc.titleThe chaperone activity of a-synuclein: Utilizing deletion mutants to map its interaction with target proteinsen_AU
dc.typeJournal Articleen_AU
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