Skip to main content
. 2013 Jan 22;110(6):2099–2104. doi: 10.1073/pnas.1219901110

Fig. 4.

Fig. 4.

Proposed antiport mechanism. Na+ (green circle) binds to a cation-free, drug-bound transporter (state 1) and elicits the movement of TM7 and TM8 (red arrow) in the cation-bound, drug-bound protein (state 2), causing the drug to dissociate. The cation-bound, drug-free transporter (state 3) then switches to the inward-facing conformation (state 4), before it binds another drug molecule (magenta). Drug-binding triggers the movement of TM7 and TM8 (red arrow), thereby weakening the Na+ binding (state 5). Na+ releases into the cytoplasm in an inward-facing, drug-bound transporter (state 6), and the transporter returns to the outward-facing, drug-bound conformation (state 1) to complete the transport cycle. Our cation-free, drug-bound NorM-NG structures (PDB ID codes 4HUK, 4HUM, and 4HUN) represent state 1, whereas the cation-bound NorM-NG (PDB ID code 4HUL) and NorM-VC structures (PDB ID codes 3MKU and 3MKT) emulate state 2 and state 3, respectively. TM1 and TM2 are simplified as a cyan stick, TM7 and TM8 as a thick yellow stick, and TM10 as a thin yellow stick.