Search

Experimentally, in the presence of crowding agent polyethylene glycol (PEG), sodium ions compact double-stranded DNA more readily than potassium ions. Here we have used molecular dynamics simulations and the “ion binding shells model” of DNA condensation to provide an atomic level picture that explains the observed variations in condensation of short (25 base pairs) DNA duplexes in solutions containing different monovalent cations and PEG; several predictions are made. In general, there are two major modes (shells) of ion binding to DNA, internal and external, distinguished by the proximity of bound ions to the helical axis. Externally bound ions contribute the most to the ion-induced aggregation of DNA duplexes. The simulations reveal that for two adjacent DNA duplexes, as well as for a single DNA duplex, the number of externally bound Na+ions is larger than the number of K+ions over a wide range of NaCl and KCl concentrations in the presence of PEG, providing a qualitative explanation for the higher propensity of sodium ions to compact DNA under crowded conditions. The qualitative picture is confirmed by an estimate of the corresponding free energy of DNA aggregation in the presence of different ions: the aggregation free energy is at least 0.2kBTper base pair more favorable in solution with NaCl than with KCl, at the same ion concentration. The estimated attraction free energy of DNA duplexes in the presence of Na+depends on the DNA sequence noticeably: we predict that AT-rich DNA duplexes are more readily condensed than GC-rich ones in the presence of Na+. The sequence dependence of the DNA aggregation propensity is nearly absent for K+. Counter-intuitively, the addition of a small amount of crowding agent with high affinity for the specific condensing ion may lead to the weakening of the ion-mediated DNA-DNA attraction, shifting the equilibrium away from the DNA condensed phase.

Ferritin is a vital protein complex responsible for storing iron in almost all living organisms. It plays a crucial role in various metabolic pathways, inflammation processes, stress response, and pathogenesis of cancer and neurodegenerative diseases. In this review we discuss the role of ferritin in diseases, cellular iron regulation, its structural features, and its role in biotechnology. We also show that molecular mechanisms of ferritin self-assembly are key for a number of biotechnological and pharmaceutical applications. The assembly pathways strongly depend on the interface context of ferritin monomers and the stability of its different intermediate oligomers. To date, several schemes of self-assembly kinetics have been proposed. Here, we compare different self-assembly mechanisms and discuss the possibility of self-assembly control by switching between deadlock intermediate states.

International audience; Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector proteins involved in signalling cascades of prokaryota and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in case of several proteins. However, this knowledge is hardly applicable to cNMP-modulated cation channels. Despite the availability of CNBD crystal structures of bacterial cyclic nucleotide-gated (CNG) and mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels in presence and absence of the cNMP, the full understanding of CNBD conformational changes during activation is lacking. Here, we describe a novel CNBD dimerization interface found in crystal structures of bacterial CNG channel MlotiK1 and mammalian cAMP-activated guanine nucleotide-exchange factor Epac2. Molecular dynamics simulations show that the found interface is stable on the studied timescale of 100 ns, in contrast to the dimerization interface, reported previously. Comparisons with cN-bound structures of CNBD show that the dimerization is incompatible with cAMP binding. Thus, the cAMP-dependent monomerization of CNBD may be an alternative mechanism of the cAMP sensing. Based on these findings, we propose a model of the bacterial CNG channel modulation by cAMP.