Related Experiment Video

Updated: Jan 20, 2026

Spatial Separation of Molecular Conformers and Clusters
10:37

Spatial Separation of Molecular Conformers and Clusters

Published on: January 9, 2014

11.7K

Transient multimers modulate conformer abundances of prion protein monomer through conformational selection

Guillaume Van der Rest1, Human Rezaei2, Frédéric Halgand3

  • 1Université Paris Sud-CNRS, Laboratoire de Chimie Physique, Bâtiment 201 P2, F-91405, Orsay, France.

Scientific Reports
|August 23, 2019
PubMed

Insights

Prion protein diseases may originate from transient multimers. Changes in prion protein structure can be transmitted via these multimers, potentially explaining disease origins and strain variations.

Area of Science:

  • Neurodegenerative diseases
  • Molecular biology
  • Protein misfolding

Background:

  • Prions, such as those implicated in Creutzfeldt-Jakob disease, are linked to neurodegenerative pathologies.
  • Current models involve a transmissible structural change producing a beta-sheet-rich prion conformer (PrPSc).
  • PrPSc triggers a self-perpetuating cascade by converting the native prion protein conformer (PrPc) into the pathogenic form.

Purpose of the Study:

  • To investigate the conformational equilibrium of recombinant prion protein (PrPc).
  • To explore the role of PrPc concentration and multimer formation in conformational selection.
  • To understand how PrPc oligomerization pathways influence conformer abundances.

Main Methods:

  • Studied recombinant PrPc in a conformational equilibrium.
  • Investigated PrPc concentration-dependent conformer abundances via transient multimer formation.
  • Analyzed PrPc mutants with distinct oligomerization pathways.

Main Results:

  • Recombinant PrPc exists in a conformational equilibrium.
  • Conformer abundances depend on PrPc concentration due to transient multimer formation and conformational selection.
  • Mutant PrPc studies confirmed that inter-conformer interactions guide oligomerization pathways.
  • These findings suggest an "aborted" oligomerization process.

Conclusions:

  • Prion protein diseases might arise from structural changes transmitted through transient multimers with varying conformer compositions.
  • This mechanism could explain the selection of specific transient multimers as precursors to PrPSc.
  • It offers a new perspective on the origin of prion diseases and the emergence of prion strains.

More Related Videos

High-Pressure NMR Experiments for Detecting Protein Low-Lying Conformational States04:37

High-Pressure NMR Experiments for Detecting Protein Low-Lying Conformational States

Published on: June 29, 2021

3.1K
Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.6K

Related Concept Videos

Conformity01:20

Conformity

Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
47.9K
Conformations of Butane02:20

Conformations of Butane

Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
17.7K
Conformations of Cycloalkanes02:29

Conformations of Cycloalkanes

Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3  hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
14.1K
Conformations of Cyclohexane02:11

Conformations of Cyclohexane

Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
15.3K
Conformations of Ethane and Propane02:18

Conformations of Ethane and Propane

In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
16.9K
Chair Conformation of Cyclohexane02:02

Chair Conformation of Cyclohexane

The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
18.0K