Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid-protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin-membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.
Honokiol (HKL) is a natural biphenolic compound derived from the bark of
magnolia trees with anti-inflammatory, anti-oxidative, anti-tumor and
neuroprotective properties. Here we show that HKL blocks agonist-induced and
pressure overload-mediated, cardiac hypertrophic responses, and ameliorates
pre-existing cardiac hypertrophy, in mice. Our data suggest that the
anti-hypertrophic effects of HKL depend on activation of the deacetylase SIRT3.
We demonstrate that HKL is present in mitochondria, enhances SIRT3 expression
nearly two-fold and suggest that HKL may bind to SIRT3 to further increase its
activity. Increased SIRT3 activity is associated with reduced acetylation of
mitochondrial SIRT3 substrates, MnSOD and OSCP. HKL-treatment increases
mitochondrial rate of oxygen consumption and reduces ROS synthesis in wild-type,
but not in SIRT3-KO cells. Moreover, HKL-treatment blocks cardiac fibroblast
proliferation and differentiation to myofibroblasts in SIRT3-dependent manner.
These results suggest that HKL is a pharmacological activator of SIRT3 capable
of blocking, and even reversing, the cardiac hypertrophic response.
Potassium channels are responsible for the selective permeation of K+ ions across cell membranes. K+ ions permeate in single file through the selectivity filter, a narrow pore lined by backbone carbonyls that compose 4 K+ binding sites. Here, we report 2D IR spectra of a semisynthetic KcsA channel with site-specific 13C18O isotope labels in the selectivity filter. The ultrafast time-resolution of 2D IR spectroscopy provides an instantaneous snapshot of the multi-ion configurations and structural distributions that occur spontaneously in the filter. Two elongated features are resolved, revealing the statistical weighting of two structural conformations. The spectra are reproduced by MD simulations of structures with water separating two K+ ions in the binding sites, ruling out configurations with ions occupying adjacent sites.
We have monitored the organization and dynamics of the hemolytic peptide melittin in membranes containing cholesterol by utilizing the intrinsic fluorescence properties of its functionally important sole tryptophan residue and circular dichroism spectroscopy. The significance of this study is based on the fact that the natural target for melittin is the erythrocyte membrane, which contains high amounts of cholesterol. Our results show that the presence of cholesterol inhibits melittin-induced leakage of lipid vesicles and the extent of inhibition appears to be dependent on the concentration of membrane cholesterol. The presence of cholesterol is also shown to reduce binding of melittin to membranes. Our results show that fluorescence parameters such as intensity, emission maximum, and lifetime of membrane-bound melittin indicate a change in polarity in the immediate vicinity of the tryptophan residue probably due to increased water penetration in presence of cholesterol. This is supported by results from fluorescence quenching experiments using acrylamide as the quencher. Membrane penetration depth analysis by the parallax method shows that the melittin tryptophan is localized at a relatively shallow depth in membranes containing cholesterol. Analysis of energy transfer results using melittin tryptophan (donor) and dehydroergosterol (acceptor) indicates that dehydroergosterol is not randomly distributed and is preferentially localized around the tryptophan residue of membrane-bound melittin, even at the low concentrations used. Taken together, our results are relevant in understanding the interaction of melittin with membranes in general, and with cholesterol-containing membranes in particular, with possible relevance to its interaction with the erythrocyte membrane.
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