FIGURE 9.

Simplified schematic model for functional dynamics within NBD1. NBD1 (dark blue) is shown as residing in two populations in a dynamic equilibrium. When channels are closed, NBD1/NBD2 heterodimers are inhibited due to the steric hindrance of the RE/R region interacting with NBD1. Addition of compound or the H620Q mutation shifts this equilibrium by reducing H9 helicity and contacts with the NBD1, subsequently leading to release of the RE/R region from the dimerization interface, relieving the inhibition and facilitating NBD1/NBD2 heterodimerization and channel opening.