Figure 5. Model for state transitions in an alternating access transporter, SemiSWEET.

TM2 of one protomer (yellow) and TM1 and TM3 of the opposing protomer (purple) are shown. The other, identical set of three helices is omitted for clarity. Gray bars represent closed extracellular and intracellular gates, and black circles represent helical packing interactions. In the outward open state (left), TM1—which, if isolated, tends to kink about a centrally located proline residue—instead assumes a straightened conformation stabilized by packing interactions with TM3. Closure of the extracellular gate, which involves a substantial motion of TM3, leads to a loss of packing interactions between TM1 and TM3. In this more ‘isolated’ environment, TM1 kinks, opening the intracellular gate. This cartoon is intended as a two-dimensional schematic rather than an accurate representation of SemiSWEET’s three-dimensional geometry. The inward motion of the extracellular end of TM3 upon closure of the extracellular gate also causes TM1 to shift slightly away from the center of the helical bundle. This smaller motion is not illustrated in the cartoon but appears to contribute to the loss of TM1–TM3 packing interactions upon extracellular gate closure.