Structural Biology of Mammalian and Non-mammalian Prion Proteins

The prion protein (PrP) is an obligatory factor in the development of transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease in humans, BSE ("mad cow disease") in cattle, and scrapie in sheep. PrP is a highly conserved glycoprotein in mammals, where it is predominantly expressed in neuronal tissue, and has also been found in birds and reptiles. We have solved the 3-dimensional structure of the recombinant "healthy" form of a wide range of mammalian and non-mammalian prion proteins. Based on the analysis of local structural similarities and differences that might bear on the function of the cellular form of PrP in healthy organisms and on the species barrier for infectious transmission of TSEs, designed variants of mouse PrP have been expressed in transgenic mice (collaboration with Prof. A. Aguzzi, University of Zürich). An apparent new strain of prions was thus generated in "RL-mice" and is further characterized using additional transgenic mouse lines that have been designed based on structural data with other variant cellular PrPs. In this context we also investigate the mechanism of the conversion of different variant cellular prion proteins into the disease-related aggregated form.

Keywords

Prion Protein, TSE, Species Barrier, Transmembrane Forms, Conversion Mechanism

Contacts

Dr. Fred Damberger, Prof. Kurt Wüthrich

Electronic Contacts

fred.damberger@mol.biol.ethz.ch
kurt.wuthrich@mol.biol.ethz.ch

In Collaboration with

Prof. A. Aguzzi and Dr. Simone Hornemann, University of Zürich, and Prof. Cristina Sigurdson, University of California San Diego, USA.

Support

ETH Zürich