Monte carlo simulations of tau proteins: effect of phosphorylation

We perform Monte Carlo simulations of tau proteins bound to a cylinder that mimics a microtubule (MT), and then study them in solution. Tau protein binds to a highly anionic MT surface to stabilize the cylindrical structure of MT. The negatively charged tail domain floats away from the anionic MT surface while positively charged tau segments localize near the MT surface. Monte Carlo simulations demonstrate that, in 3RS tau isoform (which has three imperfect repeats (R) short (S) isoform), amino acids are more condensed near a highly charged interface compared to 4RL isoform (which has four imperfect repeats (R) long (L) isoform). In 4RL isoform, amino acids in tail domain stay mostly apart from the MT surface. In the bulk solution, dephosphorylated taus are separated due to Coulomb repulsion between similarly charged isoforms. Moderate phosphorylation of 3RS isoform decreases average intermolecular distance between dephosphorylated and phosphorylated taus and lead to their overlap. Further phosphorylation does not change noticeably the intermolecular distances.     

Translational frameshift suppression in mouse mammary tumor virus and other retroviruses

Retroviruses, related retroposons, and several RNA viruses use translational frameshifting in the expression of their polymerase genes. We use retroviruses, particularly mouse mammary tumor virus, to illustrate the model which reflects our current understanding of these site-specific frameshifting events. The model has two components, a shifty sequence that facilitates ribosome slippage, and a second signal, either RNA secondary structure or an unfilled ribosomal A site, that stalls the ribosome and increases the probability of slippage at the shifty site.