Shift of fibril-forming ability of the designed alpha-helical coiled-coil peptides into the physiological pH region

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Serval ID
serval:BIB_F4229622AB4C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Shift of fibril-forming ability of the designed alpha-helical coiled-coil peptides into the physiological pH region
Journal
Protein Engineering
Author(s)
Melnik  T. N., Villard  V., Vasiliev  V., Corradin  G., Kajava  A. V., Potekhin  S. A.
ISSN
0269-2139 (Print)
Publication state
Published
Issued date
12/2003
Volume
16
Number
12
Pages
1125-30
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
Recently, we designed a short alpha-helical fibril-forming peptide (alphaFFP) that can form alpha-helical nanofibrils at acid pH. The non-physiological conditions of the fibril formation hamper biomedical application of alphaFFP. It was hypothesized that electrostatic repulsion between glutamic acid residues present at positions (g) of the alphaFFP coiled-coil sequence prevent the fibrillogenesis at neutral pH, while their protonation below pH 5.5 triggers axial growth of the fibril. To test this hypothesis, we synthesized alphaFFPs where all glutamic acid residues were substituted by glutamines or serines. The electron microscopy study confirmed that the modified alphaFFPs form nanofibrils in a wider range of pH (2.5-11). Circular dichroism spectroscopy, sedimentation, diffusion and differential scanning calorimetry showed that the fibrils are alpha-helical and have elongated and highly stable cooperative tertiary structures. This work leads to a better understanding of interactions that control the fibrillogenesis of the alphaFFPs and opens opportunities for their biomedical application.
Keywords
Calorimetry Circular Dichroism Hydrogen-Ion Concentration Microscopy, Electron Peptide Fragments/chemistry/*metabolism/ultrastructure Protein Structure, Secondary
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:55
Last modification date
25/09/2019 7:11
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