6 research outputs found
CapZ-lipid membrane interactions: a computer analysis
BACKGROUND: CapZ is a calcium-insensitive and lipid-dependent actin filament capping protein, the main function of which is to regulate the assembly of the actin cytoskeleton. CapZ is associated with membranes in cells and it is generally assumed that this interaction is mediated by polyphosphoinositides (PPI) particularly PIP(2), which has been characterized in vitro. RESULTS: We propose that non-PPI lipids also bind CapZ. Data from computer-aided sequence and structure analyses further suggest that CapZ could become partially buried in the lipid bilayer probably under mildly acidic conditions, in a manner that is not only dependent on the presence of PPIs. We show that lipid binding could involve a number of sites that are spread throughout the CapZ molecule i.e., alpha- and beta-subunits. However, a beta-subunit segment between residues 134–151 is most likely to be involved in interacting with and inserting into lipid membrane due to a slighly higher ratio of positively to negatively charged residues and also due to the presence of a small hydrophobic helix. CONCLUSION: CapZ may therefore play an essential role in providing a stable membrane anchor for actin filaments
Elucidating the mechanism of ferrocytochrome c heme disruption by peroxidized cardiolipin
The interaction of peroxidized cardiolipin with
ferrocytochrome c induces two kinetically and chemically
distinct processes. The first is a rapid oxidation of ferrocytochrome
c, followed by a slower, irreversible disruption
of heme c. The oxidation of ferrocytochrome c by peroxidized
cardiolipin is explained by a Fenton-type reaction.
Heme scission is a consequence of the radical-mediated
reactions initiated by the interaction of ferric heme iron
with peroxidized cardiolipin. Simultaneously with the
heme c disruption, generation of hydroxyl radical is
detected by EPR spectroscopy using the spin trapping
technique. The resulting apocytochrome c sediments as a
heterogeneous mixture of high aggregates, as judged by
sedimentation analysis. Both the oxidative process and the
destructive process were suppressed by nonionic detergents
and/or high ionic strength. The mechanism for generating
radicals and heme rupture is presented