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| Reference : Is Aggregation Of Beta-Amyloid Peptides A Mis-Functioning Of A Current Interaction Proce... |
| Scientific journals : Article | |||
| Life sciences : Biochemistry, biophysics & molecular biology | |||
| http://hdl.handle.net/2268/63558 | |||
| Is Aggregation Of Beta-Amyloid Peptides A Mis-Functioning Of A Current Interaction Process? | |
| English | |
| Festy, F. [> > > >] | |
Lins, Laurence  [Université de Liège > > Gembloux Agro-Bio Tech >] | |
| Peranzi, G. [> > > >] | |
| Octave, Jn. [> > > >] | |
| Brasseur, Robert [Université de Liège > > Gembloux Agro-Bio Tech >] | |
| Thomas, Annick [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér. >] | |
| 2001 | |
| Biochimica et Biophysica Acta-Protein Structure and Molecular Enzymology | |
| 1546 | |
| 2 | |
| 356-64 | |
| Yes (verified by ORBi) | |
| International | |
| 0167-4838 | |
| [en] In a previous study, Hughes et al. [Proc. Natl. Acad. Sci. USA 93 (1996)
2065-2070] demonstrated that the amyloid peptide is able to interact with itself in a two-hybrid system and that interaction is specific. They further supported that the method could be used to define the sequences that might be important in nucleation-dependent aggregation. The sequence of the amyloid peptide can be split into four clusters, two hydrophilic (1-16 and 22-28) and two hydrophobic (17-21 and 29-42). We designed by molecular modeling and tested by the two-hybrid approach, series of mutations spread all over the sequence and changing the distribution of hydrophobicity and/or the spatial hindrance. In the two-hybrid assay, interaction of native Abeta is reproduced. Screening of mutations demonstrates that the C-domain (residues 29-40 (42)), the median domain (residues 17-22) and the N-domain (1-16) are all crucial for interaction. This demonstrates that almost all fragments of the amyloid peptide but a loop (residues 23-28) and the C-term amino acid are important for the native interaction. We support that the folded three-dimensional (3D) structure is the Abeta-Abeta interacting species, that the whole sequence is involved in that 3D fold which has a low secondary structure propensity and a high susceptibility to mutations and thus should have a low stability. The native fold of Abeta could be stabilized in Abeta-Abeta complexes which could in other circumstances facilitate the nucleation event of aggregation that leads to the formation of stable senile plaques. | |
| Researchers ; Professionals | |
| http://hdl.handle.net/2268/63558 |
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