Prion Proteins pp 135-167 | Cite as

Prion Protein and Its Conformational Conversion: A Structural Perspective

  • Witold K. SurewiczEmail author
  • Marcin I. Apostol
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 305)


The key molecular event in the pathogenesis of prion diseases is the conformational conversion of a cellular prion protein, PrPC, into a misfolded form, PrPSc. In contrast to PrPC that is monomeric and α-helical, PrPSc is oligomeric in nature and rich in β-sheet structure. According to the “protein-only” model, PrPSc itself represents the infectious prion agent responsible for transmissibility of prion disorders. While this model is supported by rapidly growing experimental data, detailed mechanistic and structural aspects of prion protein conversion remain enigmatic. In this chapter we describe recent advances in understanding biophysical and biochemical aspects of prion diseases, with a special focus on structural underpinnings of prion protein conversion, the structural basis of prion strains, and generation of prion infectivity in vitro from bacterially-expressed recombinant PrP.

Graphical Abstract


Prion diseases Prion protein folding Prion strains Prion structural biology Prions 



Creutzfeldt–Jakob disease




Gerstmann–Sträussler–Scheinker disease


Hydrogen-deuterium exchange mass spectrometry


Proteinase K


Protein misfolding cyclic amplification


Prion protein


The cellular isoform of prion protein


The pathogenic or scrapie isoform of prion protein


Recombinant prion protein


Site-directed spin label


Transmissible spongiform encephalopathy



This work was supported by National Institutes of Health grants NS038604,NS044158, and AG014358.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsCase Western Reserve UniversityClevelandUSA

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