Figure 8
From: Mechanistic insights of ABC importer HutCD involved in heme internalization by Vibrio cholerae
Heme release pathway from ‘cytoplasmic gate’ to cytosol. (a) Ligand release pocket between the two dimers, HutC1–HutD1 and HutC2–HutD2 and cytoplasmic gate are shown here.TM2, TM3 of each HutC monomer are shown in pink while E92, belonging to TM2–TM3 loop is shown in red; (b) Docking of Heme near cytoplasmic gate of HutCD IF; HutC dimer is shown in electrostatic surface representation whereas HutD dimer is shown in cartoon representation. Docked heme is shown as green sticks; (c) Zoomed view showing docked heme at ‘cytoplasmic gate’ of HutC dimer of HutCD in the IF state. HutD dimer is not shown here for clarity; (d) Zoomed view showing docking of heme near ‘cytoplasmic gate’ and its interactions with HutC residues; (e) Release pathway of heme from HutCD; (f) Snapshot at 133 ns shows interaction of Heme with Q-loop and D-loop residues of HutD; (g) Interaction of heme with F151 of HutC and S136, S138 of ‘ABC signature motif’ of HutD on the verge of release to cytosol; (h) Superposition of snapshots of HutCD IF at 85, 121, 410, 468 ns. HutC and HutD subunits undergo limited fluctuations during release of heme. (i) Zoomed view of superimposed snapshots reveals noticeable conformational shift ofTM5 helices (shown as cylinder) at 410 and 468 ns (red) especially in one TMD of HutC dimer compared to 1 (grey), 85 (green), 121 (blue) ns, leading to ‘occluded’ state during heme release.
