Figure 6. Schematic diagram of the EMC regulation by VDAC1. (A) The apo conformation of the EMC denotes its role as an insertase primed for binding client TMHs. The zoom-in view shows the hydrophilic vestibule of the EMC complex. The TMH1–3 bundle and the L-shape gating plug of EMC3 are shown in light green and green respectively, and client-TMH in brown. The inside of the vestibule is positively charged as indicated. (B) The association of VDAC1 induces structural changes in the hydrophilic vestibule. The TMH1–3 bundle and the gating plug of EMC3 are shown in dark orchid and orchid, respectively. The hydrophilic vestibule is reduced and the electrostatic surface potential inside is altered to negatively charged.