Figure 3.

F233 rotates extracellularly for both activation and deactivation. (A) z-position of F233 side chain relative to Cα, averaged over 1 ns. The ring rotates upward largely along the same path for both activation and deactivation rather than merely being pushed in the translation direction. This could explain the gating kinetics differences, because the ring needs room to move upward during deactivation, whereas it can be pushed away under activation. Insets show the ring orientation for the indicated blocked/open positions. (B) Snapshot of the initial F233 orientation. The upward rotation is preferred both when R4 approaches the hydrophobic zone from above (deactivation, R_before) and below (activation, R_after). (C) The F233W side chain exhibits similar rotation behavior as WT, rotating to the extracellular side in both cases. The main difference is the R4 side chain having to make a longer flip to find room when crossing F233W.