NR AWIL
AU Kumar,J.; Vonck,J.; Glaubitz,C.; Schwalbe,H.
TI Towards an understanding of the mechanism of recombinant human prion protein amyloid formation in vitro
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-13
PT Konferenz-Poster
AB Prion diseases are fatal neurodegenerative disorders of humans and animals. These diseases can be genetic, infectious or sporadic disorders but all of these involve misfolding and aggregation of ubiquitous Prion protein (PrPc). The sequences of PrPc and PrPsc (from amyloidal plaques) are identical and a purely structural change is thought to cause aggregation and fibrillogenesis. Though NMR and X-ray structures for PrPc are determined still high resolution structure for PrPsc is unavailable. The pathways of conformational change of prion protein are poorly understood. It is believed that misfolding and aggregation of PrPc to form PrPsc have a path through partially or completely unfolded prion protein. In our lab, we have established the non-native conditions and were able to get fibril from recombinant human prion protein and synthetic peptides. The fibrils were characterized by electron microscopy and congo red absorption. NMR spectroscopy is used as primary tool to investigate the aggregation behavior of recombinant human prion protein, which is further supported by solid-state NMR spectroscopy and cryo electron microscopy. Structural preferences for recombinant human prion protein in non-native conditions are identified by H/D exchange and relaxation experiments. The behavior of neurotoxic palindrome sequence AGAAAAGA (113-120), helix 1, helix 2 and helix 3 will be discussed. They will compare with theoretical predicated models of PrPsc to describe the folding mechanism.
AD J. Kumar, H. Schwalbe: Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, Johann Wolfgang Goethe-University, Frankfurt am Main; J. Vonck: Max Planck Institute for Biophysics, Frankfurt am Main; C. Glaubitz: Institute for Biophysical Chemistry, Center for Biomolecular Magnetic Resonance, Johann Wolfgang GoetheUniversity, Frankfurt am Main
SP englisch
PO Italien