Fig. 6: Overlapping interfaces for homo- and hetero-dimerisation lead to an equilibrium that can be regulated by phosphorylation to adjust FLNC mobility.
A Plot of the distances between subunits in the homo- (orange) and heterodimer (black), as a function of sequence position in our MD simulations. The bands are defined by the closest (lower value) and average (upper value) distance over the length of the simulation (upper). The two bands overlap well, demonstrating the overall similarity of the interfaces in the two dimers. The core dimer interface is marked (dashed box), and expanded in the lower panel, which shows the average distance only, but for each of the WT, pT2677 and pY2683 simulations. These graphs show that the dimer interface distances are highly similar across the three proteins, with minor differences found only near pT2677 (for that protein). This is consistent with the overall structure of the dimer interface being largely similar, with the major differences between WT and phosphorylated forms lying in the hydrogen-bonds across the interface (Fig. 5). B Colouring residues on the surface in proportion to the closest distances of a WT FLNC monomer to its counterpart reinforces the similarity in binding site between homo- and heterodimer (insets). This allows us a simple view of the equilibria involved, where FLNCd24 homo- and hetero-dimerisation are competitive. The equilibrium favours the heterodimer for WT FLNC, and can be shifted in either direction by phosphorylation. C The shifting of the equilibrium effectively adjusts the state of FLNC, either stabilising it in the actin-crosslinking-competent homodimer form, or effectively releasing it from this role by generating the much smaller heterodimer, which is likely much more mobile in the cell.
