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Prion Proteins pp 135-167 | Cite as

Prion Protein and Its Conformational Conversion: A Structural Perspective

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

Abstract

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

Keywords

Prion diseases Prion protein folding Prion strains Prion structural biology Prions 

Abbreviations

CJD

Creutzfeldt–Jakob disease

GPI

Glycophosphatidylinositol

GSS

Gerstmann–Sträussler–Scheinker disease

HXMS

Hydrogen-deuterium exchange mass spectrometry

PK

Proteinase K

PMCA

Protein misfolding cyclic amplification

PrP

Prion protein

PrPC

The cellular isoform of prion protein

PrPSc

The pathogenic or scrapie isoform of prion protein

rPrP

Recombinant prion protein

SDSL

Site-directed spin label

TSE

Transmissible spongiform encephalopathy

Notes

Acknowledgments

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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