In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 3 ( 2005-01-18), p. 646-650
Abstract:
The NMR structure of the recombinant elk prion protein (ePrP), which represents the cellular isoform (ePrP C ) in the healthy organism, is described here. As anticipated from the highly conserved amino acid sequence, ePrP C 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 α-helices and a short antiparallel β-sheet. However, ePrP C shows a striking local structure variation when compared with most other mammalian PrPs, in particular human, bovine, and mouse PrP C . A loop of residues 166–175, which links the β-sheet with the α2-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 ePrP C relates to these two local amino acid exchanges, so that mPrP[S170N,N174T] exactly mimics ePrP C . 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0409008102
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2005
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
