Structure of the recombinant full-length hamster prion protein PrP(29–231): The N terminus is highly flexible

Abstract

The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrP C to the infectious scrapie form PrP Sc ; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these diseases develop. In this study, the secondary structure of the recom-

Prion protein structure is affected by pH‐dependent interaction with membranes: A study in a model system

“…3A. The CD spectrum displays a minimum at 208 and a shoulder at 222 nm, typical of a protein containing a large proportion of a-helical structure, and in good agreement with published CD spectra [18] and NMR data [19]. The CD spectrum of PrP in solution is pH independent.…”

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…The N-terminal domain of PrP c is a flexible "tail" compared to the C-terminal portion (Donne et al, 1997;Riek et al, 1996), N-terminal fragments are present in brains affected by scrapie and correlate with the presence of protease-resistant PrP c forms (Pan et al, 2005). In addition, aberrant N-terminal truncated forms of PrP c tethered to the cell membrane alter the response to oxidative stress and become proteaseresistant (Zeng et al, 2003).…”

“…1). The last domain or C-terminal globular domain (Donne et al, 1997;Riek et al, 1997) contains the -helix and two parallel stranded -sheets (Riek et al, 1996). PrP c presents at least three distinct topological orientations: the fully extracellular form (or (sec)PrP) (Holscher et al, 2001), and two transmembrane isoforms (called Ntm-PrP and Ctm-PrP) with opposite sequence orientations with respect to the lumen of the endoplasmic reticulum (Hegde et al, 1998).…”

Misfolding of the prion protein: linking biophysical and biological approaches

“…The structural characterization of the Nterminal as well as by NMR or CD spectroscopy reveals that this region is unfolded in solution [29]. However, four repetitions of eight amino acids called the octapeptide domain present a high affinity for Cu 2+ ions.…”

“…The first one is the nucleation model which proposes that PrP Sc exists in equilibrium with PrP C but can form oligomers acting as seeds for further polymerization [51]. The second one, known as the template-assisted model, proposes the formation of PrP C -PrP Sc heterodimers which refold into a homodimer of PrP Sc [29]. The "protein only hypothesis" represents a new paradigm of molecular biology since it implies that proteins rather than viruses or nucleic acids may be infectious and carry heritable information.…”