Histones bundle F-actin filaments and affect actin structure

Abstract

Histones are small polycationic proteins complexed with DNA located in the cell nucleus. Upon apoptosis they are secreted from the cells and react with extracellular polyanionic compounds. Actin which is a polyanionic protein, is also secreted from necrotic cells and interacts with histones. We showed that both histone mixture (histone type III) and the recombinant H2A histone bundles F-actin, increases the viscosity of the F-actin containing solution and polymerizes G-actin. The histone-actin bundles are relatively insensitive to increase of ionic strength, unlike other polycation, histatin, lysozyme, spermine and LL-37 induced F-actin bundles. The histone-actin bundles dissociate completely only in the presence of 300–400 mM NaCl. DNA, which competes with F-actin for histones, disassembles histone induced actin bundles. DNase1, which depolymerizes F- to G-actin, actively unbundles the H2A histone induced but slightly affects the histone mixture induced actin bundles. Cofilin decreases the amount of F-actin sedimented by low speed centrifugation, increases light scattering and viscosity of F-actin-histone mixture containing solutions and forms star like superstructures by copolymerizing G-actin with H2A histone. The results indicate that histones are tightly attached to F-actin by strong electrostatic and hydrophobic forces. Since both histones and F-actin are present in the sputum of patients with cystic fibrosis, therefore, the formation of the stable histone-actin bundles can contribute to the pathology of this disease by increasing the viscosity of the sputum. The actin-histone interaction in the nucleus might affect gene expression.

Buforin III Analogs Bind to DNA and Actin and Inhibit Bacterial Growth

“…Polyvalent cations bundle actin filaments [18] because the positively charged cations eliminate the repulsion between the negatively charged actin filaments [19]. As histone H2A, the parent molecule of buforin, also bundles actin [8], and the formation of actin bundles can have pathological consequences [20], it was of interest to study the interaction between buforin III derivatives and actin. Buforin IIIB and IIIE are polyvalent cations each containing eight extra positive charges.…”

“…DNA and Binding of Buforin IIIB and IIIE to DNA Polyanions dissociate polycation-induced actin filament bundles as polyanions compete with negatively charged Factin for polycations. DNA, which is a highly negatively charged polyanion, was shown to unbundle histone-induced actin bundles [8]. We studied the effect of DNA on buforin III analog-induced F-actin bundles with low speed centrifugation ( Figure 6), as the buforin-DNA complex, unlike the F-actin-buforin complex, is not sedimented under this condition.…”

“…Histones, including histone H2A and its buforin derivatives, possess antimicrobial activity [5][6][7] that is based on interactions with the microbial membrane. Histones also react with other negatively charged particles, including actin filaments, which can be bundled by histones [8]. Buforin II is a smaller derivative of buforin and is produced from buforin by treatment with the endoproteinase Lys-C. Its antimicrobial activity is significantly higher than that of the parent molecule [9].…”

Interaction of Extracellular Histones with DNA and Actin Filaments

“…We showed that histone mixture H3 (histone type III) and H2A histone bundle Factin, increase the viscosity of the F-actin containing solutions and polymerize G-actin [14]. The histone mixture-actin bundles are dissociated by DNA and 300-400 mM NaCl [14]. The histone-actin bundles are highly stable.…”

“…Extracellular histones have a bad side too, they act as inflammatory agents [13], major mediators of death in sepsis [13] and have a significant role in tissue injury and inflammation [5]. We showed that histone mixture H3 (histone type III) and H2A histone bundle Factin, increase the viscosity of the F-actin containing solutions and polymerize G-actin [14]. The histone mixture-actin bundles are dissociated by DNA and 300-400 mM NaCl [14].…”