Solid-state NMR reveal structural differences between wild-type and disease-related A53T mutan fibrils of alpha-synuclein.

HEISE H, CELEJ MS, BECKER S, RIEDEL D, PELAH A, KUMAR A, JOVIN TM, BALDUS M.

JOURNAL OF MOLECULAR BIOLOGY

Academic Press

Lugar: Inglaterra; Año: 2008 vol. 380 p. 444 - 450

0022-2836

Fibrils from the Parkinson´s-disease-related A53T mutant of α-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 β- strand character, in addition to the rigid β-sheet-rich core region. As in earlier studies on wild-type α-synuclein, the C-terminus was found to be flexible and unfolded, whereas the main core region was highly rigid and rich in β-sheets. Compared to fibrils from wild-type α-synuclein, the wellordered β-sheet region extends to at least L38 and L100. These results demonstrate that a disease-related mutant of α-synuclein differs in both aggregation kinetics and fibril structure.