Figure 1.

The Putative Open-State Structure of dOrai and the “Twist-to-Open” Gating Motion

(A) A representative open-state structure of the wild-type dOrai pore (abbreviated as wt_o, where TM1–TM4 are in green, yellow, blue, and red, respectively) aligned with its X-ray structure in the closed state (abbreviated as wt_c, which is shown in silver, PDB entry: 4HKR). Key residues lining the pore are shown in stick mode.

(B and C) Superposition between wt_c (in gray) and wt_o (in red and blue) pores, where only TM1 helices are shown in space-filling mode. Views from the extracellular (B) and intracellular (C) sides of the pore highlight the different directions of rotation during gating (shown by arrow). The dashed line connects Cα atoms of Q152 on alternate chains, representing different motions of neighboring TM1 at the N-terminal side.

(D) The calculated I-V relationship of the wt_o structure.

(E and F) Calculated potential of mean force (PMF) for cation permeation through the pore. (E) The one-dimensional PMFs of wt_o (in blue), wt_c (in red), and the V174A mutant (in green), showing that the open state is energetically favorable for ion flux. (F) The two-dimensional profile of the wt_o further suggests a zigzag pathway for ion permeation along the pore. The x axis shows the distance away from the pore axis; the y axis is along the pore axis.