Reference : Structural And Functional Properties Of The 154-171 Wild-Type And Variant Peptides Of...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/63742
Structural And Functional Properties Of The 154-171 Wild-Type And Variant Peptides Of Human Lecithin-Cholesterol Acyltransferase
English
Peelman, F. [> > > >]
Goethals, M. [> > > >]
Vanloo, B. [> > > >]
Labeur, C. [> > > >]
Brasseur, Robert mailto [Université de Liège > > Gembloux Agro-Bio Tech >]
Vandekerckhove, J. [> > > >]
Rosseneu, M. [> > > >]
1997
European Journal of Biochemistry
249
3
708-15
Yes (verified by ORBi)
0014-2956
[en] The 154-171 segment of the human lecithin-cholesterol acyltransferase (LCAT)
enzyme was identified as the most stable amphipathic helix in the LCAT sequence.
Its mean hydrophobicity, hydrophobic moment and its orientation at a lipid/water
interface are similar to those of some of the helical repeats of apolipoprotein
A-IV and E. This domain was therefore proposed as a candidate peptide accounting
for the association between LCAT and its lipid substrate. To investigate this
hypothesis we synthesized the LCAT-(154-171)-peptide, two variants containing the
natural Y156N and R158C mutations and a variant with increased hydrophobicity
through Y156I, L160I, L163I and Y171W substitutions. The structural and
lipid-binding properties of these synthetic peptides were investigated by
turbidity, fluorescence, electron microscopy and circular dichroism. The
wild-type peptide, the R158C variant in its dimeric form, as well as the more
hydrophobic peptide, associated with phospholipids, whereas the Y156N and the
R158C variant in its monomeric form did not. However, only the complexes
generated with the hydrophobic variant were stable enough to resist dissociation
during gel filtration. The wild-type peptide and hydrophobic variant formed
discoidal complexes with dimyristoylglycerophosphocholine (Myr2GroPCho) as shown
by negative staining electron microscopy. Comparison of the properties of the
wild-type and hydrophobic variant LCAT-(154-171)-peptide stresses the
contribution of the hydrophobic face of the amphipathic helix to the formation
and stabilization of the peptide/lipid complexes. This is further confirmed by
the decreased affinity of the Y156N variant peptide for lipids, as this mutation
decreased the mean hydrophobicity of the hydrophobic face of the amphipathic
helix. These results support the hypothesis that the 154-171 segment of LCAT
might be involved in the interaction of the enzyme with its lipid substrate and
suggest that the decreased activity of the Y156N natural LCAT mutant might result
from a decreased affinity of this mutant for lipids.
Researchers ; Professionals
http://hdl.handle.net/2268/63742

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