| First Author | Christen B | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 21 | Pages | 8549-54 |
| PubMed ID | 23650394 | Mgi Jnum | J:197446 |
| Mgi Id | MGI:5492315 | Doi | 10.1073/pnas.1306178110 |
| Citation | Christen B, et al. (2013) Structural plasticity of the cellular prion protein and implications in health and disease. Proc Natl Acad Sci U S A 110(21):8549-54 |
| abstractText | Two lines of transgenic mice expressing mouse/elk and mouse/horse prion protein (PrP) hybrids, which both form a well-structured beta2-alpha2 loop in the NMR structures at 20 degrees C termed rigid-loop cellular prion proteins (RL-PrP(C)), presented with accumulation of the aggregated scrapie form of PrP in brain tissue, and the mouse/elk hybrid has also been shown to develop a spontaneous transmissible spongiform encephalopathy. Independently, there is in vitro evidence for correlations between the amino acid sequence in the beta2-alpha2 loop and the propensity for conformational transitions to disease-related forms of PrP. To further contribute to the structural basis for these observations, this paper presents a detailed characterization of RL-PrP(C) conformations in solution. A dynamic local conformational polymorphism involving the beta2-alpha2 loop was found to be evolutionarily preserved among all mammalian species, including those species for which the WT PrP forms an RL-PrP(C). The interconversion between two ensembles of PrP(C) conformers that contain, respectively, a 310-helix turn or a type I beta-turn structure of the beta2-alpha2 loop, exposes two different surface epitopes, which are analyzed for their possible roles in the still evasive function of PrP(C) in healthy organisms and/or at the onset of a transmissible spongiform encephalopathy. |
