Cdt holotoxin preferentially binds to LUVs containing cholesterol.
The interaction of Cdt holotoxin with LUVs containing varying amounts of
cholesterol was analyzed by FRET and SPR. Panel A shows FRET analysis
of Cdt with LUVs containing varying amounts (10–40 mol %) cholesterol.
Values are the mean ± S.D. (n = 3), expressed as relative %
energy transfer. Results are statistically significant (p < 0.05;
multivariant analysis of variance with post-hoc Scheffe test) for differences
in energy transfer as cholesterol concentration is increased. Panel B
shows the SPR results of Cdt interaction with LUVs. An overlay of sensorgrams
shows the interaction of Cdt (10 μg/ml) with immobilized LUVs containing
decreasing concentrations of cholesterol; data points were collected every 0.2
s. Data are plotted as response units versus time and are
representative of three experiments. Panel C shows the results of SPR
analysis for the interaction of two concentrations of Cdt (10 and 20 μg/ml)
with immobilized LUVs containing 5, 10, and 20% cholesterol; data are the mean
± S.D. of three experiments and are plotted as the number of response
units obtained from each sensorgram after 3 min post-injection. Results are
statistically significant (p < 0.29; multivariant analysis of
variance) for differences in response units as toxin concentration is
increased. Panel D shows the results of SPR analysis of Cdt (20
μg/ml) with immobilized LUVs containing 20% of either cholesterol,
lanosterol, ergosterol, or stigmasterol. The mean ± S.D. of the maximum
response is plotted for three experiments. Results are statistically
significant for differences between cholesterol and lanosterol (p
< 0.001), cholesterol and ergosterol (p = 0.029), and cholesterol
and stigmasterol (p = 0.029). To verify that liposomes contained
comparable levels of sterol, aliquots of liposomes were extracted, and the
amount of sterol was determined as described in
Fig. 1; extraction yields were
7.9 μg (lanosterol), 8.6 μg (ergosterol), 7.6 μg (stigmasterol), and
7.8 μg (cholesterol).