The Antemortem Detection and Conformational Switches of Prion Proteins

2005 ◽  
Author(s):  
David R. Schubert ◽  
Yuanbin Liu ◽  
Roland Riek
Keyword(s):  
Prion Proteins ◽  
Conformational Switches

Rapid Quantification of Prion Proteins

2019 ◽  
Author(s):  
Matthew Healey ◽  
Muttuswamy Sivakumaran ◽  
Mark Platt
Keyword(s):  
Prion Proteins ◽  
Prion Diseases ◽  
Sample Volume ◽  
Cellular Prion Protein ◽  
Dna Aptamer ◽  
Superparamagnetic Beads ◽  
Resistive Pulse ◽  
Large Sample Volume ◽  
Complex Sample ◽  
Neurological Conditions

<p>Prion diseases are a group of fatal transmissible neurological conditions caused by the change in conformation of the normal intrinsic cellular prion protein (PrP<sup>C</sup>) in to the highly ordered insoluble amyloid state conformer (PrP<sup>SC</sup>). We present a rapid assay using Aptamers and Resistive Pulse Sensing, RPS, to extract and quantify proteins from complex sample matrices, demonstrate with the quantification of PrP<sup>c</sup>. We functionalise the surface of superparamagnetic beads, SPBs, with a DNA aptamer. First SPB’s termed P-Beads, are used to pre-concentrate the analyte from a large sample volume. The PrP<sup>c</sup> protein is then eluted from the P-Beads before aptamer modified sensing beads, S-Beads, are added. The velocity of the S-Beads through the nanopore reveals the concentration of the PrP<sup>c</sup> protein. The process is done in under an hour and allows the detection of picomol’s of protein. The technique could be easily adopted to the mutated version of the protein and integrated into clinical workflows for the screening of blood donations and transfusions. </p>

Prion proteins: Physiological functions and role in neurological disorders

2008 ◽  
Vol 264 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Wei Hu ◽  
Bernd Kieseier ◽  
Elliot Frohman ◽  
Todd N. Eagar ◽  
Roger N. Rosenberg ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Prion Proteins ◽  
Physiological Functions

Distinct prion proteins in short and long scrapie incubation period mice

Cell ◽  
1987 ◽  
Vol 51 (4) ◽  
pp. 651-662 ◽  
Author(s):  
David Westaway ◽  
Patricia A. Goodman ◽  
Carol A. Mirenda ◽  
Michael P. McKinley ◽  
George A. Carlson ◽  
...  
Keyword(s):  
Incubation Period ◽  
Prion Proteins

scholarly journals Chimeric elk/mouse prion proteins in transgenic mice

2013 ◽  
Vol 94 (2) ◽  
pp. 443-452 ◽  
Author(s):  
Gültekin Tamgüney ◽  
Kurt Giles ◽  
Abby Oehler ◽  
Natrina L. Johnson ◽  
Stephen J. DeArmond ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Prion Proteins ◽  
Second Line ◽  
Mouse Line ◽  
Wasting Disease ◽  
C Terminus ◽  
Incubation Periods ◽  
N Terminus ◽  
Mouse Lines

Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). Between codons 169 and 219, six residues distinguish ElkPrP from MoPrP: N169S, T173N, V183I, I202V, I214V and R219K. Using chimeric elk/mouse PrP constructs, we generated 12 Tg mouse lines and determined incubation times after intracerebral inoculation with the mouse-passaged RML scrapie or Elk1P CWD prions. Unexpectedly, one Tg mouse line expressing Elk3M(SNIVVK) exhibited incubation times of <70 days when inoculated with RML prions; a second line had incubation times of <90 days. In contrast, mice expressing full-length ElkPrP had incubation periods of >250 days for RML prions. Tg(Elk3M,SNIVVK) mice were less susceptible to CWD prions than Tg(ElkPrP) mice. Changing three C-terminal mouse residues (202, 214 and 219) to those of elk doubled the incubation time for mouse RML prions and rendered the mice resistant to Elk1P CWD prions. Mutating an additional two residues from mouse to elk at codons 169 and 173 increased the incubation times for mouse prions to >300 days, but made the mice susceptible to CWD prions. Our findings highlight the role of C-terminal residues in PrP that control the susceptibility and replication of prions.

scholarly journals Prion protein dynamics before aggregation

2017 ◽  
Vol 114 (14) ◽  
pp. 3572-3577 ◽  
Author(s):  
Kinshuk Raj Srivastava ◽  
Lisa J. Lapidus
Keyword(s):  
Protein Dynamics ◽  
Neurodegenerative Disorders ◽  
Syrian Hamster ◽  
Time Scale ◽  
Molecular Basis ◽  
Prion Proteins ◽  
Prion Diseases ◽  
Hydrophobic Residues ◽  
Protein Deposits ◽  
Polypeptide Backbone

Prion diseases, like Alzheimer’s disease and Parkinson disease, are rapidly progressive neurodegenerative disorders caused by misfolding followed by aggregation and accumulation of protein deposits in neuronal cells. Here we measure intramolecular polypeptide backbone reconfiguration as a way to understand the molecular basis of prion aggregation. Our hypothesis is that when reconfiguration is either much faster or much slower than bimolecular diffusion, biomolecular association is not stable, but as the reconfiguration rate becomes similar to the rate of biomolecular diffusion, the association is more stable and subsequent aggregation is faster. Using the technique of Trp–Cys contact quenching, we investigate the effects of various conditions on reconfiguration dynamics of the Syrian hamster and rabbit prion proteins. This protein exhibits behavior in all three reconfiguration regimes. We conclude that the hamster prion is prone to aggregation at pH 4.4 because its reconfiguration rate is slow enough to expose hydrophobic residues on the same time scale that bimolecular association occurs, whereas the rabbit sequence avoids aggregation by reconfiguring 10 times faster than the hamster sequence.

Coupling ligand structure to specific conformational switches in the β2-adrenoceptor

2006 ◽  
Vol 2 (8) ◽  
pp. 417-422 ◽  
Author(s):  
Xiaojie Yao ◽  
Charles Parnot ◽  
Xavier Deupi ◽  
Venkata R P Ratnala ◽  
Gayathri Swaminath ◽  
...  
Keyword(s):  
Ligand Structure ◽  
Conformational Switches
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