NR AOQP
AU Bonjour,S.; Lysek,D.A.; Gossert,A.; Wüthrich,K.
TI CWD and PrP structure: Model studies with recombinant variants of murine PrP.
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-111
PT Konferenz-Poster
AB Beside the more notorious transmissible spongiform encephalopathies (TSEs) scrapie in sheep and bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) in captive and free-ranging cervids has recently attracted high attention. All these prion diseases have been shown to be related to the presence of the cellular form of the prion protein (PrPc). The three-dimensional structures of several recombinant mammalian prion proteins (PrPs) have been solved. Although they all show the same global fold, the length and regularity of the a-helix 3 and the NMR-observability of the residues in the loop comprising residues 166-172, have been found to show high species variability. Furthermore, experiments with transgenic laboratory animals indicated that these molecular regions may be involved in specific interactions influencing the TSE-related conformational transition of PrP. In the elk PrP structure, the loop connecting the second b-strand and the a-helix 2 exhibits no detectable conformational exchange. A trend toward a uniquely structured form of this loop has been observed for the recombinant Syrian hamster PrP (shPrP) and the human PrP mutant (hPrP[S170N]). Here we attempt to relate this conformational feature to specific amino acid exchanges. The elk PrP sequence contains a unique amino acid substitution, N174T, which has now been introduced into mouse PrP. In order to address the question of the importance of the amino acid substitutions within this loop region, we present nuclear magnetic resonance measurements yielding the solution structure of the globular domain of the resulting variant mouse PrP.
AD S. Bonjour, D.A. Lysek, A. Gossert, K. Wüthrich, Eidgenössische Technische Hochschule Zürich, Switzerland
SP englisch
PO Deutschland