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Updated: May 12, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 6, 2013

Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions

Heidi Olzscha1, Sonya M Schermann, Andreas C Woerner

  • 1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany.

Cell
|January 11, 2011
PubMed

Insights

Artificial protein aggregates cause disease by disrupting essential cellular functions. This study reveals that toxic aggregates sequester large, unstructured proteins, leading to multifactorial cellular collapse and neurodegeneration.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Protein aggregation, particularly amyloid-like fibril formation, is implicated in neurodegeneration and other diseases.
  • The precise mechanisms driving the toxicity of these aggregates remain poorly understood.

Purpose of the Study:

  • To investigate the gain-of-function toxicity of artificial β sheet proteins designed to form amyloid-like fibrils.
  • To identify the cellular targets and pathways affected by these toxic protein aggregates.

Main Methods:

  • Quantitative proteomics was employed to analyze protein interactions and cellular responses.
  • Artificial β sheet proteins were designed to form amyloid-like fibrils in human cells.

Main Results:

  • Aggregate toxicity correlated with the promotion of aberrant protein interactions and deregulation of the cytosolic stress response.
  • Endogenous proteins sequestered by aggregates were large, enriched in unstructured regions, and functionally multifunctional.
  • Interacting proteins included essential hubs involved in chromatin organization, transcription, translation, cell architecture, and protein quality control.

Conclusions:

  • Amyloidogenic aggregation targets a specific subproteome characterized by large size and unstructured regions.
  • This targeting leads to multifactorial toxicity by disrupting essential cellular networks.
  • The collapse of these critical cellular functions contributes to disease pathogenesis.

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