NR AXPL
AU Julien,O.; Sykes,B.D.
TI Investigation of Prions Structure and Stability by NMR
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.74
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of fatal neurological diseases of humans and animals characterized by memory and cognitive disturbances. At the end of the twentieth century, the bovine spongiform encephalopathy (BSE), better known as mad cow disease, has been proved to be transmissible to humans. This brought a lot of concern for public health and a lot of questions for scientists. There are two major forms of prion protein: the native and noninfectious form (PrPc), which corresponds mainly to an alpha-helix structure, and the misfolded infectious form, corresponding to an assembly of beta-sheet forming amyloid fibrils (PrPsc). The solution structure of the non-infectious form of the mouse prion protein (121-231) was determined in 1996. Since then, about 30 structures of the globular portion of PrPc have been characterized for different organisms (mostly from mammals). However, only a few minor differences are noticeable from comparing one structure to another. The key to understanding prion formation may then not be hidden in the structure of PrPc, but more likely in a hypothetical transition state. But how is the normal prion protein (PrPc) converted into an unfolding fibril state (PrPsc)? To identify the possible regions required/responsible for amyloid fibril formation, we are using NMR methods to characterize the stability of PrPc and the transition state between PrPc and PrPsc. We hope to get local structural information about the prion conversion, which seems to be the source of prion infectivity.
AD O. Julien, B.D. Sykes, University of Alberta, Department of Biochemistry, Canada
SP englisch
PO Schottland