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NMR Structure of the Bank Vole Prion Protein at 20 °C Contains a Structured Loop of Residues 165–171


Christen, Barbara; Perez, Daniel Raoul; Hornemann, Simone; Wüthrich, Kurt (2008). NMR Structure of the Bank Vole Prion Protein at 20 °C Contains a Structured Loop of Residues 165–171. Journal of Molecular Biology, 383(2):306-312.

Abstract

The recent introduction of bank vole (Clethrionomys glareolus) as an additional laboratory animal for research on prion diseases revealed an important difference when compared to the mouse and the Syrian hamster, since bank voles show a high susceptibility to infection by brain homogenates from a wide range of diseased species such as sheep, goats, and humans. In this context, we determined the NMR structure of the C-terminal globular domain of the recombinant bank vole prion protein (bvPrP) [bvPrP(121–231)] at 20 °C. bvPrP(121–231) has the same overall architecture as other mammalian PrPs, with three α-helices and an antiparallel β-sheet, but it differs from PrP of the mouse and most other mammalian species in that the loop connecting the second β-strand and helix α2 is precisely defined at 20 °C. This is similar to the previously described structures of elk PrP and the designed mouse PrP (mPrP) variant mPrP[S170N,N174T](121–231), whereas Syrian hamster PrP displays a structure that is in-between these limiting cases. Studies with the newly designed variant mPrP[S170N](121–231), which contains the same loop sequence as bvPrP, now also showed that the single-amino-acid substitution S170N in mPrP is sufficient for obtaining a well-defined loop, thus providing the rationale for this local structural feature in bvPrP.

Abstract

The recent introduction of bank vole (Clethrionomys glareolus) as an additional laboratory animal for research on prion diseases revealed an important difference when compared to the mouse and the Syrian hamster, since bank voles show a high susceptibility to infection by brain homogenates from a wide range of diseased species such as sheep, goats, and humans. In this context, we determined the NMR structure of the C-terminal globular domain of the recombinant bank vole prion protein (bvPrP) [bvPrP(121–231)] at 20 °C. bvPrP(121–231) has the same overall architecture as other mammalian PrPs, with three α-helices and an antiparallel β-sheet, but it differs from PrP of the mouse and most other mammalian species in that the loop connecting the second β-strand and helix α2 is precisely defined at 20 °C. This is similar to the previously described structures of elk PrP and the designed mouse PrP (mPrP) variant mPrP[S170N,N174T](121–231), whereas Syrian hamster PrP displays a structure that is in-between these limiting cases. Studies with the newly designed variant mPrP[S170N](121–231), which contains the same loop sequence as bvPrP, now also showed that the single-amino-acid substitution S170N in mPrP is sufficient for obtaining a well-defined loop, thus providing the rationale for this local structural feature in bvPrP.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Structural Biology
Life Sciences > Molecular Biology
Uncontrolled Keywords:Molecular Biology
Language:English
Date:1 November 2008
Deposited On:10 Nov 2020 15:51
Last Modified:17 Nov 2020 16:42
Publisher:Elsevier
ISSN:0022-2836
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.jmb.2008.08.045
PubMed ID:18773909

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