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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-53806

Damberger, F F; Christen, B; Pérez, D R; Hornemann, S; Wüthrich, K (2011). Cellular prion protein conformation and function. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 108(42):17308-17313.

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Abstract

In the otherwise highly conserved NMR structures of cellular prion proteins (PrP(C)) from different mammals, species variations in a surface epitope that includes a loop linking a β-strand, β2, with a helix, α2, are associated with NMR manifestations of a dynamic equilibrium between locally different conformations. Here, it is shown that this local dynamic conformational polymorphism in mouse PrP(C) is eliminated through exchange of Tyr169 by Ala or Gly, but is preserved after exchange of Tyr 169 with Phe. NMR structure determinations of designed variants of mouse PrP(121-231) at 20 °C and of wild-type mPrP(121-231) at 37 °C together with analysis of exchange effects on NMR signals then resulted in the identification of the two limiting structures involved in this local conformational exchange in wild-type mouse PrP(C), and showed that the two exchanging structures present characteristically different solvent-exposed epitopes near the β2-α2 loop. The structural data presented in this paper provided a platform for currently ongoing, rationally designed experiments with transgenic laboratory animals for renewed attempts to unravel the so far elusive physiological function of the cellular prion protein.

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15 citations in Web of Science®
13 citations in Scopus®
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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
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:14 Jan 2012 18:00
Last Modified:09 Jan 2014 09:56
Publisher:National Academy of Sciences
ISSN:0027-8424
Publisher DOI:10.1073/pnas.1106325108
PubMed ID:21987789

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