NR ARNB

AU Gossert,A.D.; Bonjour,S.; Lysek,D.A.; Fiorito,F.; Wüthrich,K.

TI Prion protein NMR structures of elk and of mouse/elk hybrids

QU Proceedings of the National Academy of Sciences of the United States of America 2005 Jan 18; 102(3): 646-50

IA http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=545551

PT journal article

AB The NMR structure of the recombinant elk prion protein (ePrP), which represents the cellular isoform (ePrPc) in the healthy organism, is described here. As anticipated from the highly conserved amino acid sequence, ePrPc has the same global fold as other mammalian prion proteins (PrPs), with a flexibly disordered "tail" of residues 23-124 and a globular domain 125-226 with three alpha-helices and a short antiparallel beta-sheet. However, ePrPc shows a striking local structure variation when compared with most other mammalian PrPs, in particular human, bovine, and mouse PrPc. A loop of residues 166-175, which links the beta-sheet with the alpha2-helix and is part of a hypothetical "protein X" epitope, is outstandingly well defined, whereas this loop is disordered in the other species. Based on NMR structure determinations of two mouse PrP variants, mPrP[N174T] and mPrP[S170N,N174T], this study shows that the structured loop in ePrPc relates to these two local amino acid exchanges, so that mPrP[S170N,N174T] exactly mimics ePrPc. These results are evaluated in the context of recent reports on chronic wasting disease (CWD) in captive and free-ranging deer and elk in the U.S. and Canada, and an animal model is proposed for support of future research on CWD.

MH Animals; Mice; Mutation, Missense; *Nuclear Magnetic Resonance, Biomolecular; Prions/*chemistry/genetics; Protein Conformation; Protein Structure, Secondary; Recombinant Proteins/chemistry/genetics; Research Support, Non-U.S. Gov't; Ruminants; Species Specificity; Structural Homology, Protein; Wasting Disease, Chronic/etiology

AD Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Zürich, CH-8093 Zürich, Switzerland.

SP englisch

PO USA

EA pdf-Datei

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