Gerstmann-Sträussler-Scheinker disease amyloid protein polymerizes according to the "dock-and-lock" model

J Biol Chem. 2006 Jan 13;281(2):843-9. doi: 10.1074/jbc.M506164200. Epub 2005 Nov 10.


Prion protein (PrP) amyloid formation is a central feature of genetic and acquired prion diseases such as Gerstmann-Sträussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues approximately 82-146, which when synthesized as a peptide, readily forms fibrils featuring GSS amyloid. The present study employed surface plasmon resonance (SPR) to characterize the binding events underlying PrP82-146 oligomerization at the first stages of fibrillization, according to evidence suggesting a pathogenic role of prefibrillar oligomers rather than mature amyloid fibrils. We followed in real time the binding reactions occurring during short term (seconds) addition of PrP82-146 small oligomers (1-5-mers, flowing species) onto soluble prefibrillar PrP82-146 aggregates immobilized on the sensor surface. SPR data confirmed very efficient aggregation/elongation, consistent with the hypothesis of nucleation-dependent polymerization process. Much lower binding was observed when PrP82-146 flowed onto the scrambled sequence of PrP82-146 or onto prefibrillar Abeta42 aggregates. As previously found with Abeta40, SPR data could be adequately fitted by equations modeling the "dock-and-lock" mechanism, in which the "locking" step is due to sequential conformational changes, each increasing the affinity of the monomer for the fibril until a condition of irreversible binding is reached. However, these conformational changes (i.e. the locking steps) appear to be faster and easier with PrP82-146 than with Abeta40. Such differences suggest that PrP82-146 has a greater propensity to polymerize and greater stability of the aggregates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Animals
  • Cricetinae
  • Epitopes
  • Gerstmann-Straussler-Scheinker Disease / metabolism*
  • Humans
  • Kinetics
  • Microscopy, Electron
  • Models, Chemical
  • Peptides / chemistry
  • Polymers / chemistry
  • Protein Binding
  • Protein Denaturation
  • Protein Folding
  • Surface Plasmon Resonance
  • Surface Properties
  • Time Factors


  • Amyloid
  • Epitopes
  • Peptides
  • Polymers