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-tumour 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 twofold 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 oligomycin-sensitivity conferring protein (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 a Sirt3-dependent manner. These results suggest that HKL is a pharmacological activator of Sirt3 capable of blocking, and even reversing, the cardiac hypertrophic response.

Signaling through the kinase Akt regulates many biological functions. Akt is activated during growth factor stimulation through a process that requires binding of Akt to phosphatidylinositol 3,4,5-trisphosphate (PIP₃), which promotes membrane localization and phosphorylation of Akt by the upstream kinase PDK1 (phosphoinositide-dependent protein kinase 1). We show that Akt and PDK1 are acetylated at lysine residues in their pleckstrin homology domains, which mediate PIP₃ binding. Acetylation blocked binding of Akt and PDK1 to PIP₃, thereby preventing membrane localization and phosphorylation of Akt. Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP₃ and promoted their activation. Mice injected with cells expressing a mutant that mimicked a constitutively acetylated form of Akt developed smaller tumors than those injected with cells expressing wild-type Akt. Furthermore, impaired Akt activation in the hearts of SIRT1-deficient mice was associated with reduced cardiac hypertrophy in response to physical exercise and angiotensin II. These findings uncover a key posttranslational modification of Akt that is important for its oncogenic and hypertrophic activities.

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 four K ⁺ binding sites. Here, we report on the two-dimensional infrared (2D IR) spectra of a semisynthetic KcsA channel with site-specific heavy ( ¹³ C ¹⁸ O) 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 molecular dynamics simulations of structures with water separating two K ⁺ ions in the binding sites, ruling out configurations with ions occupying adjacent sites.