NMR structure of the mouse prion protein domain PrP(121–231)

  title={NMR structure of the mouse prion protein domain PrP(121–231)},
  author={Roland Riek and Simone Hornemann and Gerhard Wider and Martin Billeter and Rudi Glockshuber and Kurt W{\"u}thrich},
THE 'protein only' hypothesis1 states that a modified form of normal prion protein triggers infectious neurodegenerative diseases, such as bovine spongiform encephalopathy (BSE), or Creutzfeldt–Jakob disease (CJD) in humans2–4. Prion proteins are thought to exist in two different conformations5: the 'benign' PrPC form, and the infectious 'scrapie form', PrPSc. Knowledge of the three-dimensional structure of PrPC is essential for understanding the transition to PrPSc. The nuclear magnetic… 

NMR Structure of the Human Prion Protein with the Pathological Q212P Mutation Reveals Unique Structural Features

The NMR solution structure of the truncated recombinant human PrP from residue 90 to 231 carrying the Q212P mutation, which is believed to cause Gerstmann-Sträussler-Scheinker (GSS) syndrome, a familial prion disease, is described.

The crystal structure of the globular domain of sheep prion protein.

Molecular architecture of human prion protein amyloid: A parallel, in-register β-structure

The data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrPC involves major refolding of the C-terminal α-helical region, which has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases.

Prion protein NMR structure and species barrier for prion diseases.

The structural basis of species specificity of transmissible spongiform encephalopathy or "mad cow disease" and Creutzfeldt-Jakob disease in humans has been investigated using the refined NMR structure of the C-terminal domain of the mouse prion protein with residues 121-231.

The roles of the conserved tyrosine in the β2-α2 loop of the prion protein

The role of a tyrosine residue (Y169) which is strictly conserved in mammalian PrPs is analyzed and it emerges that Y169 is an aggregation gatekeeper with a twofold role.

The prion protein globular domain and disease-related mutants studied by molecular dynamics simulations.

The fact that some of the disease-related amino acid exchanges cause no measurable change of the PrP(C) structure indicates that their influence on the conformational transition to the scrapie form of PrP may be due to modified intermolecular interactions during the aggregation process.

Structural plasticity of the cellular prion protein and implications in health and disease

A dynamic local conformational polymorphism involving the β2–α2 loop was found to be evolutionarily preserved among all mammalian species, including those species for which the WT PrP forms an RL-PrPC.

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

  • D. DonneJ. H. Viles H. Dyson
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
Backbone dynamics studies done by using the heteronuclear [1H]-15N nuclear Overhauser effect indicate that almost half of PrP(29-231), residues 29-124, is highly flexible, which could feature in the conversion of PrPC to PrPSc by template-assisted formation of beta-structure.

Peptides and proteins in neurodegenerative disease: helix propensity of a polypeptide containing helix 1 of the mouse prion protein studied by NMR and CD spectroscopy.

Transmissible spongiform encephalopathies (TSE) or "prion diseases" have been related to the "protein-only hypothesis", which suggests that the "scrapie form (PrPSc)" of the prion protein (PrP) is



Proposed three-dimensional structure for the cellular prion protein.

The three-dimensional structure of PrPc proposed here may not only provide a basis for rationalizing mutations of the PrP gene in the inherited prion diseases but also guide design of genetically engineered PrP molecules for further experimental studies.

Prions and prion proteins 1

  • N. StahlS. Prusiner
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1991
The amino acid sequence and posttranslational modifications of PrPSc and its proteolytically truncated core PrP 27‐30 are analyzed to identify potential candidate modifications that could distinguish PrP sc from PrPC.

Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.

  • K. PanM. Baldwin F. Cohen
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
It is argued that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, and it is likely that this conformational transition is a fundamental event in the propagation of prions.

Prion protein (PrP) with amino‐proximal deletions restoring susceptibility of PrP knockout mice to scrapie.

This work has introduced into PrP knockout mice transgenes encoding wild‐type PrP or PrP lacking 26 or 49 amino‐proximal amino acids which are protease susceptible in PrP(Sc), and found thatoculation with prions led to fatal disease, prion propagation and accumulation of PrP (Sc) in mice expressing both wild‐ type and truncated PrPs.

Prion protein is necessary for normal synaptic function

It is argued that loss of function of PrPc may contribute to the early synaptic loss3 and neuronal degeneration seen in Creutzfeldt–Jakob disease and scrapie and bovine spongiform encephalopathy in animals.

Genetic and infectious prion diseases.

Bioassays of brain extracts from two scrapie-infected Tg lines showed that the prion inoculum determines that prions are synthesized de novo, even though the cells express both PrP genes, and underscore the fundamental features of prion structure and propagation that differentiate prions from other transmissible pathogens.

Molecular biology of prion diseases

Understanding prion diseases may advance investigations of other neurodegenerative disorders and of the processes by which neurons differentiate, function for decades, and then grow senescent.