Optimization of hydrophobic domains in peptides that undergo transformation from alpha-helix to beta-fibril.
Recent studies on peptide fibrillogenesis by the de novo method as well as amyloidogenic proteins including prion proteins and Alzheimer's beta-peptides have provided insights into the conformational changes, such as alpha-helix to beta-structure, involved in folding and misfolding processes. We have found that an exposed hydrophobic nucleation domain at N-terminal causes a structural transition of a peptide from alpha-helix to beta-fibril. It became clear that N-terminal acyl groups of particular lengths in a 2alpha-helix peptide caused the peptide to undergo an alpha-to-beta transition. The peptide with the octanoyl group (C8-2alpha) showed the highest rate of transformation. The study of the designed peptides revealed that these alpha-to-beta transitions were closely related to the initial alpha-helix conformation and its stability. Engineering peptides that undergo alpha-to-beta transitions are attractive not only to the study of pathogenic proteins such as prion proteins, but also to the control of self-assembly of peptides, which will lead to the development of peptidyl self-assembling materials.
Takahashi
Y
Y
Department of Bioengineering, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Ueno
A
A
Mihara
H
H
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003902:Detergents / Q000494:pharmacology; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D003902:Detergents; D010455:Peptides