Research Paper Volume 16, Issue 6 pp 5501—5525

Figure 5. Conformational changes during the transition between the apo- and VDAC1-bound EMC. (A) Comparison of the hydrophilic cavities in the apo and VDAC1-bound EMC. The cavities are shown as surface representation in light blue, and EMC3 and EMC7 in ribbon, with TMH^EMC7, TMH2^EMC3 and EMC3^188–210 segment colored in green, orchid and dark orchid, respectively. (B) Conformational change of EMC3^188–210 segment, the gating plug, between the apo and VDAC1-bound states. This segment forms an L-shape architecture (cyan) in the apo EMC state, whereas it folds back around Gly188 to form an open circular loop (orchid), held against the TMH_1–3 bundle of EMC3 in the VDAC1-bound state. (C) Left: the intramolecular interactions of EMC3 that stabilize the gating plug in the VDAC1-bound state. Hydrogen bonds are indicated by dashed lines. Right: electrostatic surface potential of the same region. (D) Residues Arg31, Arg180 and Asn117 on the TMH_1–3 bundle of EMC3 form a conserved positively charged patch inside the EMC hydrophilic vestibule in the apo state. (E) Electrostatic surface potential of the EMC3 gating plug. The location of hydrophilic cavity is indicated by a dashed circle. (F) Conformational change of TMH2^EMC3 between the apo and VDAC1-bound states. In the apo EMC (cyan), TMH2^EMC3 is only partially ordered (α1). In the VDAC1-bound state (orchid), the entire TMH2^EMC3 (α1 and α2) is visible.