Pierced Lasso Bundles Are a New Class of Knot-like Motifs
Figure 7
Native state dynamics of leptin, hGH, IFNϕ-1 and hIL-3.
Structure based all-atom simulations were performed to obtain NSD. Data for reduced and oxidized protein are shown in blue and red, respectively. The overall fluctuations are shown as bar graphs and the difference between the two states is plotted as a yellow line. The protein sequence is displayed at the top of the graphs and a cartoon of secondary structures is displayed at the bottom (indicating the position of the N- versus the C-terminal loop in light blue and dark blue respectively). Leptin shows an interesting shift in dynamics where the oxidized state is more dynamic than the reduced state over the majority of the structure. The disulphide bridge, not only closes the covalent loop, but also acts as a point of tension inducing dynamics, far from the disulphide bridge. Helix A in leptin shows increased dynamics in the oxidized state, opposite to what is observed in the other PLBs. The decreased dynamics in helix A for the other PLBs is a result of the disulphide bride pining down helix A, thus restricting its dynamics. Interestingly helix A in hIL-3 completely unfolds in the native basin in the reduced state (the data dwarfs the effects on the rest of the sequence and is not included in this figure for clarity). hGH is has an “empty” covalent loop (a “cinch” like structure) of about 100 residues. The plot for hGH shows no significant change of the overall dynamics between reduced and oxidized protein, except for the expected local effect around the disulphide bridge. This implies that that the formation of the covalent loop alone has no effect on the NSD while the presence of a threaded topology piercing the lasso changes the entire protein dynamics.