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J. Biol. Chem., Vol. 276, Issue 18, 14628-14633, May 4, 2001
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From the Vibrio cholerae cytolysin
(VCC) forms oligomeric pores in lipid bilayers containing cholesterol.
Membrane permeabilization is inefficient if the sterol is embedded
within bilayers prepared from phosphatidylcholine only but is greatly
enhanced if the target membrane also contains ceramide. Although the
enhancement of VCC action is stereospecific with respect to
cholesterol, we show here that no such specificity applies to the two
stereocenters in ceramide; all four stereoisomers of ceramide enhanced
VCC activity in cholesterol-containing bilayers. A wide variety of
ceramide analogs were as effective as
D-erythro-ceramide, as was diacylglycerol, suggesting that the effect of ceramide exemplifies a general trend of
lipids with a small headgroup to augment the activity of VCC. Incorporation of these cone-shaped lipids into cholesterol-containing bilayers also gave similar effects with streptolysin O, another cholesterol-specific but structurally unrelated cytolysin. In contrast,
the activity of staphylococcal
Coupling of Cholesterol and Cone-shaped Lipids in Bilayers
Augments Membrane Permeabilization by the Cholesterol-specific Toxins
Streptolysin O and Vibrio cholerae Cytolysin*
,
,
,
, and
¶
Institute of Medical Microbiology and
Hygiene, University of Mainz, Obere Zahlbacher Strasse 67, D55101
Mainz, Germany, and § Department of Chemistry and
Biochemistry, Queens College of The City University of New York,
Flushing, New York 11367-1597
-hemolysin, which does not share with
the other toxins the requirement for cholesterol, was far less affected
by the presence of lipids with a conical shape. The collective data
indicate that sphingolipids and glycerolipids do not interact with the
cytolysins specifically. Instead, lipids that have a conical molecular
shape appear to effect a change in the energetic state of membrane
cholesterol that in turn augments the interaction of the sterol
with the cholesterol-specific cytolysins.
*
This study was supported by the Deutsche
Forschungsgemeinschaft (SFB 490) and by the National Institutes of
Health (Grant HL-16660).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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