Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

doi:10.1080/19336896.2015.1084464

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

Journal Article · Tue Sep 01 04:00:00 EDT 2015 · Prion

DOI:https://doi.org/10.1080/19336896.2015.1084464· OSTI ID:1404953

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH

OSTI ID:: 1404953

Journal Information:: Prion, Journal Name: Prion Journal Issue: 5 Vol. 9; ISSN 1933-6896

Country of Publication:: United States

Language:: ENGLISH

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