Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle
Figure 4
Time evolution of key molecular events during the passage from OF to IF state and release of substrate and Na+ ions.
Release involves destabilization of interactions near N21 (tan) and TM1a tilting. (A) Alignment of TM1 and TM6 in the OFo (orange) and IFo (blue) crystal structures showing the reorientation of TM1a. N21, S256 (green) and S355 (red) are displayed in vdW spheres (OFo) and wildframe (IFo). Time evolutions of (B) N21-S256 (green) and N21-S355 (red) distances, based on residue mass centers; (C) TM1a tilting angle relative to the normal to membrane plane; (D) distance between TM1a (R11-A22) and TM6b (F259-Y268) residue mass centers; and (E) z-coordinates (see panel F) of Ala, Na1 and Na2, released at ∼50, 80 and 240 ns, respectively. (F) LeuT IFo conformation at 100 ns. TM1a is colored cyan. Arrows show the principal mode 1 deduced from essential dynamics analysis of cMD run 8. Gray vertical bar at 7.4 ns marks the switch from tMD (run 3) to cMD (run 8).