Reference : Contribution Of The Hydrophobicity Gradient Of An Amphipathic Peptide To Its Mode Of Ass...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Contribution Of The Hydrophobicity Gradient Of An Amphipathic Peptide To Its Mode Of Association With Lipids
Perez-Mendez, O. [> > > >]
Vanloo, B. [> > > >]
Decout, A. [> > > >]
Goethals, M. [> > > >]
Peelman, F. [> > > >]
Vandekerckhove, J. [> > > >]
Brasseur, Robert mailto [Université de Liège > > Gembloux Agro-Bio Tech >]
Rosseneu, M. [> > > >]
European Journal of Biochemistry
Yes (verified by ORBi)
[en] A class of peptides that associate with lipids, known as oblique-orientated
peptides, was recently described [Brasseur R., Pillot, T., Lins, L.,
Vandekerckhove, J. & Rosseneu, M. (1997) Trends Biochem. Sci. 22, 167-171]. Due
to an asymmetric distribution of hydrophobic residues along the axis of the
alpha-helix, such peptides adopt an oblique orientation which can destabilise
membranes or lipid cores. Variants of these oblique peptides, designed to have an
homogeneous distribution of hydrophobic and hydrophilic residues along the
helical axis, are classified as regular amphipathic peptides. These peptides are
expected to lie parallel to the polar/apolar interface with their hydrophobic
residues directed towards the apolar and their hydrophilic residues towards the
polar phase. An hydrophobic, oblique-orientated peptide was identified at
residues 56-68 in the sequence of the lecithin-cholesterol acyltransferase
(LCAT), enzyme. This peptide is predicted to penetrate a lipid bilayer at an
angle of 40 degrees through its more hydrophobic C-terminal end and thereby
induce the destabilisation of a membrane or a lipid core. The LCAT-(56-68)
wild-type peptide was synthesised together with the LCAT-(56-68, 0 degrees)
variant, in which the hydrophobicity gradient was abolished through residue
permutations. In two other variants, designed to keep their oblique orientation,
the W61 residue was shifted either towards the more hydrophilic N-terminal at
residue 57, or to position 68 at the hydrophobic C-terminal end of the peptide.
Peptide-induced vesicle fusion was demonstrated by fluorescence measurements
using pyrene-labeled vesicles and by monitoring of vesicle size by gel
filtration. The interaction between peptides and lipids was monitored by
measurement of the intrinsic tryptophan fluorescence emission of the peptides.
Fluorescence polarisation measurements, using diphenyl hexatriene, were carried
out to follow changes in the lipid fluidity. The LCAT-(56-68) wild-type peptide
and the two oblique variants, induced fusion of unilamellar
dimyristoylglycerophosphocholine vesicles. Tryptophan fluorescence emission
measurements showed a 12-14 nm blue shift upon addition of the wild-type peptide
and of the W61-->68 variant to lipids, whereas the fluorescence of the W61-->57
variant did not change significantly. This observation supports the insertion of
the more hydrophobic C-terminal residues into the lipid phase, as predicted by
the theoretical calculations. In contrast, the 0 degrees variant peptide had no
fusogenic activity, and it associated with lipids to form small discoidal
lipid/peptide complexes. The phospholipid transition temperature was decreased
after addition of the wild-type, the W61-->68 and W61-->57 fusogenic peptides,
whereas the opposite effect was observed with the 0 degrees variant. The
behaviour of the wild-type and variant LCAT-(56-68) peptides stresses the
contribution of the hydrophobicity gradient along the axis of an amphipathic
peptide to the mode of association of this peptide with lipids. This parameter
consequently influences the structural modifications occurring to lipids upon
association with amphipathic peptides.
Researchers ; Professionals

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