FIGURE 12.

Model for bimodal regulation of Vps4 and ESCRT function by Ist1. A, model of Ist1 conformations and their effects on Vps4 regulation. In the semi-open Ist1 conformation, the Ist1 MIM element (M, blue box) and ELYC region (E, pink box) interact with Vps4 to inhibit ATPase activity. Unfolding of the Ist1 core domain in a more open conformation permits Vps4 hyperstimulation in a MIM-dependent manner. Did2 induces the conversion between Ist1 inhibitory and stimulatory activities, presumably through generating the open conformation of Ist1. B, effects of Ist1 concentration on Vps4 regulation. Ist1 incorporates into ESCRT-III via Did2, leading to an open Ist1 conformation (circle) and stimulation of Vps4-mediated ESCRT-III disassembly (green arrow). Saturation of ESCRT-III with Ist1 leads to the accumulation of soluble Ist1 in a closed conformation (square), resulting in inhibition of Vps4-mediated ESCRT-III disassembly (red line).