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Updated: Aug 11, 2026
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Amyloid and the Cross-Beta Architecture
Published on: February 13, 2026
Peripheral region for core cross-beta plays important role in amyloidogenicity
Hisayuki Morii1, Masatoshi Saiki, Takeo Konakahara
1National Institute of Advanced Industrial Science and Technology (AIST), AIST Central 6, Tsukuba, Ibaraki 305-8566, Japan. morii.hi@aist.go.jp
Biochemical and Biophysical Research Communications
|February 28, 2006
Summary
The peripheral amino acid sequence near the amyloid core significantly influences amyloid formation and fibril stability. Specific sequences, like Leu-Ser-Leu, promote higher amyloidogenicity and dictate molecular packing.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Amyloid fibrils are protein aggregates implicated in various diseases.
- The role of sequences flanking the amyloid core remains incompletely understood.
- Understanding these peripheral sequences is crucial for deciphering amyloid formation mechanisms.
Purpose of the Study:
- To investigate the impact of N-terminal peripheral sequences on amyloid formation.
- To determine the specific amino acid preferences and sequence motifs driving amyloidogenicity.
- To elucidate how peripheral sequences influence fibril structure and stability.
Main Methods:
- Construction of a peptide library with all Lys, Glu, Ser, Leu combinations at N-terminal positions (X1-X3).
- Analysis of 64 peptides using Circular Dichroism (CD) spectra and thioflavin T binding assays.
- Classification of amyloidogenic peptides based on thioflavin T fluorescence wavelength.
Main Results:
- Both amino acid composition and specific sequence in the peripheral region are critical for amyloid formation.
- Amino acid preference order: Leu ≈ Ser > Glu >> Lys.
- A balance of positive and negative charges is essential for fibril stability, indicating the importance of electrostatic interactions.
- Two distinct sequence preferences, (Leu, Ser/Glu, Leu) and (Glu, Leu, Ser), were identified for highly amyloidogenic peptides.
- The peripheral sequence regulates molecular packing within fibrils and influences amyloidogenicity.
Conclusions:
- Peripheral sequences play a significant role in modulating amyloid formation and fibril structure.
- Electrostatic interactions mediated by charged residues in the peripheral region are vital for fibril stability.
- The identified sequence motifs provide insights into the structural basis of amyloid formation and thioflavin T binding.
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