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Updated: Aug 15, 2026
07:14
Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
Published on: February 25, 2022
The amyloid stretch hypothesis: recruiting proteins toward the dark side
Alexandra Esteras-Chopo1, Luis Serrano, Manuela López de la Paz
1European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Summary
Short protein segments drive amyloid fibril formation. Identifying these "amyloid stretches" offers new therapeutic targets for amyloid-related disorders by inhibiting protein self-assembly.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Amyloid fibrils are linked to various diseases.
- Protein self-association into fibrils is complex.
- Amino acid side chains significantly influence fibril formation.
Purpose of the Study:
- To validate the amyloid stretch hypothesis.
- To investigate the role of specific protein sequences in amyloidogenesis.
- To identify potential therapeutic targets for amyloid disorders.
Main Methods:
- Protein engineering by inserting amyloidogenic sequences.
- Assessing the conversion of soluble proteins into amyloidogenic forms.
- Analyzing the structural components of resulting amyloid fibrils.
Main Results:
- A six-residue amyloidogenic insertion triggered fibril formation in a soluble protein.
- The protease-resistant core of fibrils included inserted sequences and adjacent native sequences.
- Short, accessible amyloid stretches initiate self-assembly and recruit surrounding protein regions.
Conclusions:
- Amyloidogenicity is localized in specific, short protein stretches.
- These "amyloid stretches" act as nucleation sites for fibril formation.
- Targeting these stretches could inhibit amyloid fibril formation and treat related diseases.
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