Fibril fragments from the amyloid core of lysozyme: An accelerated molecular dynamics study

Protein aggregation and formation of amyloid fibrils are associated with many diseases and present a ubiquitous problem in protein science. Hen egg white lysozyme (HEWL) can form fibrils both from the full length protein and from its fragments. In the present study, we simulated unfolding of the amyloidogenic fragment of HEWL encompassing residues 49–101 to study the conformational aspects of amyloidogenesis. The accelerated molecular dynamics approach was used to speed up the sampling of the fragment conformers under enhanced temperature. Analysis of conformational transformation and intermediate structures was performed. During the unfolding, the novel short-living and long-living β-structures are formed along with the unstructured random coils. Such β-structure enriched monomers can interact with each other and propagate into fibril-like forms. The stability of oligomers assembled from these monomers was evaluated in the course of MD simulations with explicit water. The residues playing a key role in fibril stabilization were determined. The work provides new insights into the processes occurring at the early stages of amyloid fibril assembly

Interaction-induced structural transformation of lysozyme and kappa-carrageenan in binary complexes

The interactions between κ-carrageenan and hen egg-white lysozyme have been studied. In dilute solutions, the insoluble complexes with constant κ-carrageenan/lysozyme ratio of 0.3, or 12 disaccharide units per mole of protein are formed. FTIR-spectroscopy revealed that κ-carrageenan retains its unordered conformation and induces the rise of β-structure in lysozyme. In the complexes formed in concentrated mixtures, κ-carrageenan adopts helical conformation and lysozyme retains its native-like structure. These complexes contain 21 disaccharide units per mole of protein. Molecular modeling showed that flexible coil and rigid double helix of κ-carrageenan have different binding patterns to lysozyme surface. The latter has a strong preference to positively charged spots in lysozyme α-domain while the former also interacts to protein β-domain and stabilizes short-living β-structures. The obtained results confirm the preference of unordered κ-carrageenan to β-structure rich protein regions, which can be further used in the development of carrageenan-based protection of amyloid-like aggregation of proteins

Interaction of bovine serum albumin with cationic imidazolium-containing amphiphiles bearing urethane fragment: Effect of hydrophobic tail length

© 2020 Complexation ability of homologous series of amphiphiles bearing imidazolium and urethane moieties (IAC-n, n = 14, 16, 18) toward bovine serum albumin (BSA) has been investigated by various physico-chemical methods (tensiometry, fluorescence spectroscopy, spectrophotometry, dynamic and electrophoretic light scattering, circular dichroism, and transmission electron microscopy). It has been revealed, that aggregation thresholds of systems based on IAC-n could be 5–8-fold reduced by BSA addition. Fluorescent analysis allows to estimate that binding of components is favorably mediated by tryptophan amino acid residues and is driven by different forces depending on the length of amphiphile hydrophobic tail. In particular, dominate contribution of Van der Waals interactions to the complexation has been shown in the case of IAC-14 and IAC-16, while hydrophobic interactions prevailed for IAC-18. It has been demonstrated that amphiphile addition causes reversible unfolding of protein macromolecules in all cases. Spectrophotometry assay exhibits that amphiphile/BSA complexes have more significant solubilization capacity toward hydrophobic guest in comparison with individual IAC-n systems

Pillar[5]arenes as potential personage for DNA compactization and gene therapy

© 2020 Elsevier B.V. Here we demonstrated that pillar[5]arenes with counterions I− and Cl− show the ability to plasmid compactization and increasing bacterial transformation efficiently. Pillar[5]arenes have been tested for binding with palindromic decamer oligonucleotide and interacting with plasmid DNA. The complexation of pillar[5]arene with oligonucleotide has been shown by NMR- and CD-spectroscopy. Pillar[5]arenes form complexes with oligonucleotide in solution in the 1:1 or 1:2 stoichiometry. Molecular modeling allowed to constructs the models of these complexes. Pillar[5]arene interaction with the plasmid DNA have been studied using atomic force microscopy. According to AFM images pillar[5]arene-I− and pillar[5]arene-Cl− packed up the plasmid DNA to aggregates with diameter about 100 nm with different morphology. An increase in DNA transformation efficiency into bacterial cells has been shown for pillar[5]arenes with counterions I− and Cl−