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.
Highlights
Actin is the most important structural protein in the cell with multiple functions [1]
We found that several factors, including ionic strength, cofilin, DNase1 and deoxyribonucleic acid (DNA) affect the structure and stability of the histone induced F-actin bundles
Due to its severing effect cofilin dissociates bundles because of the decreased affinity of shorter actin filaments to react with each other, as we found studying the effect of cofilin on polylysine, spermine, lysozyme [2] and LL-37 [10] induced actin bundles
Summary
Actin is the most important structural protein in the cell with multiple functions [1]. There are two forms of actin: the globular G-actin, which is monomer and the polymer F-actin, both forms are negatively charged. In the cell actin exists mainly in F-form. Monovalent, divalent and polyvalent cations including cationic proteins and peptides polymerize G-actin to F-actin. Charged polycationic proteins and peptides bundle F-actin via non-.
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