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Please use this identifier to cite or link to this item: http://apo.ansto.gov.au/dspace/handle/10238/4346

Title: The chaperone activity of a-synuclein: Utilizing deletion mutants to map its interaction with target proteins
Authors: Rekas, A
Ahn, KJ
Kim, J
Carver, JA
Keywords: MUTANTS
LIGHT SCATTERING
Agglomeration
Crystalline Lens
PHYSIOLOGY
Heat-shock proteins
Issue Date: 1-Mar-2012
Publisher: Wiley-Blackwell
Citation: Rekas, 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.
Abstract: a-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.
URI: http://dx.doi.org/10.1002/prot.24028
http://apo.ansto.gov.au/dspace/handle/10238/4346
ISSN: 0887-3585
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