Journal Article

PreJuSER-276

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant alpha-synuclein

Heise, H.FZJ* ; Celej, M. S. ; Becker, S. ; Riedel, D. ; Pelah, A. ; Kumar, A. ; Jovin, T. M. ; Baldus, M.

2008
Elsevier Amsterdam [u.a.]

This record in other databases:      

Please use a persistent id in citations: doi:10.1016/j.jmb.2008.05.026

Abstract: 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.

Keyword(s): Amino Acid Sequence (MeSH) ; Escherichia coli: genetics (MeSH) ; Freezing (MeSH) ; Humans (MeSH) ; Microscopy, Atomic Force (MeSH) ; Microscopy, Electron (MeSH) ; Molecular Sequence Data (MeSH) ; Mutation (MeSH) ; Nuclear Magnetic Resonance, Biomolecular: methods (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: pathology (MeSH) ; Protein Structure, Secondary (MeSH) ; Recombinant Proteins: chemistry (MeSH) ; Recombinant Proteins: metabolism (MeSH) ; Recombinant Proteins: ultrastructure (MeSH) ; alpha-Synuclein: chemistry (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; alpha-Synuclein: ultrastructure (MeSH) ; Recombinant Proteins ; alpha-Synuclein ; J ; solid-state NMR (auto) ; amyloid (auto) ; Parkinson's disease (auto) ; alpha-synuclein (auto) ; AFM (auto)

Note: Record converted from VDB: 12.11.2012

---

Contributing Institute(s):

1. Molekulare Biophysik (INB-2)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)

Appears in the scientific report 2008

---