Reference : Fusogenic Properties Of The C-Terminal Domain Of The Alzheimer Beta-Amyloid Peptide
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Fusogenic Properties Of The C-Terminal Domain Of The Alzheimer Beta-Amyloid Peptide
Pillot, T. [> > > >]
Goethals, M. [> > > >]
Vanloo, B. [> > > >]
Talussot, C. [> > > >]
Brasseur, Robert mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Vandekerckhove, J. [> > > >]
Rosseneu, M. [> > > >]
Lins, Laurence mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Journal of Biological Chemistry
Yes (verified by ORBi)
[en] A series of natural peptides and mutants, derived from the Alzheimer beta-amyloid
peptide, was synthesized, and the potential of these peptides to induce fusion of
unilamellar lipid vesicles was investigated. These peptide domains were
identified by computer modeling and correspond to respectively the C-terminal
(e.g. residues 29-40 and 29-42) and a central domain (13-28) of the beta-amyloid
peptide. The C-terminal peptides are predicted to insert in an oblique way into a
lipid membrane through their N-terminal end, while the mutants are either
parallel or perpendicular to the lipid bilayer. Peptide-induced vesicle fusion
was demonstrated by several techniques, including lipid-mixing and core-mixing
assays using pyrene-labeled vesicles. The effect of peptide elongation toward the
N-terminal end of the entire beta-amyloid peptide was also investigated. Peptides
corresponding to residues 22-42 and 12-42 were tested using the same techniques.
Both the 29-40 and 29-42 beta-amyloid peptides were able to induce fusion of
unilamellar lipid vesicles and calcein leakage, and the amyloid 29-42 peptide was
the most potent fusogenic peptide. Neither the two mutants or the 13-28
beta-amyloid peptide had any fusogenic activity. Circular dichroism measurements
showed an increase of the alpha-helical content of the two C-terminal peptides at
increasing concentrations of trifluoroethanol, which was accompanied by an
increase of the fusogenic potential of the peptides. Our data suggest that the
alpha-helical content and the angle of insertion of the peptide into a lipid
bilayer are critical for the fusogenic activity of the C-terminal domain of the
amyloid peptide. The differences observed between the fusogenic capacity of the
amyloid 29-40 and 29-42 peptides might result from differences in the degree of
penetration of the peptides into the membrane and the resulting membrane
destabilization. The longer peptides, residues 22-42 and 12-42, had decreased,
but significant, fusogenic properties associated with perturbation of the
membrane permeability. These data suggest that the fusogenic properties of the
C-terminal domain of the beta-amyloid peptide might contribute to the
cytotoxicity of the peptide by destabilizing the cell membrane.
Researchers ; Professionals

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