Fig. 8. Potential mechanisms.

a Location of sybody binding sites on the LRR domain of LRRC8A. The proteins are shown as ribbon with different sybodies labeled. b Schematic depiction of a potential modulatory mechanism of channel function by sybody binding. Binding of inhibitory sybodies to the convex outside of the LRR domains (left) reduces flexibility of the domains, which stabilizes a closed channel conformation. Conversely, the binding of activating sybodies to the concave inside increases domain mobility, which is in some way transmitted to the pore region to open the ion conduction path.