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1: J Mol Biol. 2008 Jul 11;380(3):444-50. Epub 2008 May 17.
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Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant alpha-synuclein.

Heise H, Celej MS, Becker S, Riedel D, Pelah A, Kumar A, Jovin TM, Baldus M.

Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Solid-State NMR Group, Am Fassberg 11, D-37077 Göttingen, Germany. h.heise@fz-juelich.de

Fibrils from the Parkinson's-disease-related A53T mutant of alpha-synuclein were investigated by solid-state NMR spectroscopy, electron microscopy, and atomic force microscopy. Sequential solid-state NMR resonance assignments were obtained for a large fraction of the fibril core. Experiments conducted above and below the freezing point suggest that the fibrils contain regions with increased mobility and structural elements different from beta-strand character, in addition to the rigid beta-sheet-rich core region. As in earlier studies on wild-type alpha-synuclein, the C-terminus was found to be flexible and unfolded, whereas the main core region was highly rigid and rich in beta-sheets. Compared to fibrils from wild-type alpha-synuclein, the well-ordered beta-sheet region extends to at least L38 and L100. These results demonstrate that a disease-related mutant of alpha-synuclein differs in both aggregation kinetics and fibril structure.

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PMID: 18539297 [PubMed - indexed for MEDLINE]