Gerald Stubbs
Last active: 2/15/2016

Structural studies of truncated forms of the prion protein PrP.

Wan W, Wille H, Stöhr J, Kendall A, Bian W, McDonald M, Tiggelaar S, Watts JC, Prusiner SB, Stubbs G
Biophys J. 2015 108 (6): 1548-1554

PMID: 25809267 · PMCID: PMC4375555 · DOI:10.1016/j.bpj.2015.01.008

Prions are proteins that adopt self-propagating aberrant folds. The self-propagating properties of prions are a direct consequence of their distinct structures, making the understanding of these structures and their biophysical interactions fundamental to understanding prions and their related diseases. The insolubility and inherent disorder of prions have made their structures difficult to study, particularly in the case of the infectious form of the mammalian prion protein PrP. Many investigators have therefore preferred to work with peptide fragments of PrP, suggesting that these peptides might serve as structural and functional models for biologically active prions. We have used x-ray fiber diffraction to compare a series of different-sized fragments of PrP, to determine the structural commonalities among the fragments and the biologically active, self-propagating prions. Although all of the peptides studied adopted amyloid conformations, only the larger fragments demonstrated a degree of structural complexity approaching that of PrP. Even these larger fragments did not adopt the prion structure itself with detailed fidelity, and in some cases their structures were radically different from that of pathogenic PrP(Sc).

Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

MeSH Terms (14)

Amyloid Animals Brain Escherichia coli GPI-Linked Proteins Humans Mice Mice, Transgenic Microscopy, Electron Nerve Tissue Proteins Prions Protein Conformation Recombinant Proteins X-Ray Diffraction

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