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Autonomous and reversible folding of a soluble amino-terminally truncated segment of the mouse prion protein

S Hornemann1, R Glockshuber

  • 1Institut für Molekularbiologie und Biophysik Eidgenössische Technische Hochschule Hönggerberg, Zürich, Switzerland.

Journal of Molecular Biology
|September 6, 1996
PubMed

Insights

Researchers studied prion protein folding, finding a soluble segment (PrP 121-231) that folds reversibly. This discovery aids understanding of prion diseases and the cellular prion protein (PrPc) to infectious prion (PrPsc) conversion.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Prion diseases involve the misfolding of the cellular prion protein (PrPc) into an infectious form (PrPsc).
  • Understanding PrPc/PrPsc conversion requires studying prion protein folding and stability.
  • Low solubility of prion proteins hinders structural and thermodynamic studies.

Purpose of the Study:

  • To investigate the folding properties of a soluble, amino-terminally truncated mouse prion protein segment (PrP 121-231).
  • To determine if PrP 121-231 is an autonomous folding unit and assess its stability.
  • To provide insights into the structural basis of PrPc to PrPsc conversion.

Main Methods:

  • Expression and purification of recombinant mouse PrP 121-231.
  • Solubility assays in distilled water.
  • Guanidinium chloride-induced equilibrium unfolding/refolding experiments.
  • Circular dichroism spectroscopy to analyze secondary structure.

Main Results:

  • PrP 121-231 is soluble at high concentrations (up to 1 mM) in distilled water.
  • The segment exhibits predominantly alpha-helical secondary structure.
  • PrP 121-231 undergoes a cooperative, reversible folding transition with a free energy of folding of -22 kJ/mol at pH 7.
  • The stability of PrP 121-231 challenges current models of PrPc and PrPsc structure.

Conclusions:

  • PrP 121-231 functions as an autonomous folding unit.
  • This soluble segment may represent the structured domain of PrPc.
  • Findings offer a new avenue for studying prion protein folding and disease mechanisms.

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