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Salient Features of Monomeric Alpha-Synuclein Revealed by NMR Spectroscopy

Overview
Journal Biomolecules
Publisher MDPI
Date 2020 Mar 14
PMID 32164323
Citations 9
Authors
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Abstract

Elucidating the structural details of proteins is highly valuable and important for the proper understanding of protein function. In the case of intrinsically disordered proteins (IDPs), however, obtaining the structural details is quite challenging, as the traditional structural biology tools have only limited use. Nuclear magnetic resonance (NMR) is a unique experimental tool that provides ensemble conformations of IDPs at atomic resolution, and when studying IDPs, a slightly different experimental strategy needs to be employed than the one used for globular proteins. We address this point by reviewing many NMR investigations carried out on the α-synuclein protein, the aggregation of which is strongly correlated with Parkinson's disease.

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References
1.
Kirschner D, Abraham C, Selkoe D . X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proc Natl Acad Sci U S A. 1986; 83(2):503-7. PMC: 322888. DOI: 10.1073/pnas.83.2.503. View

2.
Bertoncini C, Jung Y, Fernandez C, Hoyer W, Griesinger C, Jovin T . Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proc Natl Acad Sci U S A. 2005; 102(5):1430-5. PMC: 547830. DOI: 10.1073/pnas.0407146102. View

3.
Radhakrishnan I, Parker D, Dyson H, Montminy M, Wright P . Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions. Cell. 1997; 91(6):741-52. DOI: 10.1016/s0092-8674(00)80463-8. View

4.
Conway K, Harper J, Lansbury Jr P . Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry. 2000; 39(10):2552-63. DOI: 10.1021/bi991447r. View

5.
Wu K, Kim S, Fela D, Baum J . Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation. J Mol Biol. 2008; 378(5):1104-15. PMC: 3064448. DOI: 10.1016/j.jmb.2008.03.017. View