English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Burial of the polymorphic residue 129 in amyloid fibrils of prion stop mutants.

MPS-Authors
/persons/resource/persons15837

Skora,  L.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons79054

Fonseca,  L.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15710

Riedel,  D.
Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons36496

Giller,  K.
Department of NMR-Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons14824

Becker,  S.
Department of NMR-Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons16093

Zweckstetter,  M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

External Resource

http://www.jbc.org/content/288/5/2994.full.pdf+html?sid=2cbe42d5-a573-42bb-b840-547817f623e7
(Publisher version)

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

1586811.pdf
(Publisher version), 3MB

Supplementary Material (public)

1586811-Suppl.pdf
(Supplementary material), 219KB

Citation

Skora, L., Fonseca, L., Hofele, R. V., Riedel, D., Giller, K., Watzlawik, J., et al. (2013). Burial of the polymorphic residue 129 in amyloid fibrils of prion stop mutants. Journal of Biological Chemistry, 288(5), 2994-3002. doi:10.1074/jbc.M112.423715 jbc.M112.423715.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0010-8FBF-7
Abstract
Misfolding of the natively alpha-helical prion protein into a beta-sheet rich isoform is related to various human diseases such as Creutzfeldt-Jakob disease and Gerstmann-Straeussler-Scheinker-like syndrome. In humans the disease phenotype is modified by a methionine/valine polymorphism at codon 129 of the prion protein gene. Using a combination of H/D exchange coupled to NMR spectroscopy, hydroxyl radical probing detected by mass spectrometry and site-directed mutagenesis we demonstrate that stop mutants of the human prion protein have a conserved amyloid core. The 129 residue is deeply buried in the amyloid core structure and its mutation strongly impacts aggregation. Taken together the data support a critical role of the polymorphic residue 129 of the human prion protein in aggregation and disease.