Figure 1. The quiescent conformation –latched with a closed pore.

(a) Overall structure of Orai, from PDB ID 4HKR, in a ‘quiescent’ conformation (Hou et al., 2012). The pore is closed; M4-ext helices pair with one another. The M1 helices are depicted as blue ribbons; other helices are cylinders. The approximate boundaries of the plasma membrane are shown as gray bars. Regions referred to as ‘latches’ in this study are indicated as dashed ovals. (b) Close-up view of the closed pore. Two M1 helices are drawn as ribbons (four M1 helices are omitted for clarity). The pore is a depicted as a gray surface indicating the minimal radial distance to the nearest van der Waals contact. Amino acid side chains that form the walls of the pore are drawn as sticks and colored (yellow for carbon, blue for nitrogen, and red for oxygen). Amino acid numbering is shown for Drosophila melanogaster Orai without parentheses and for human Orai in parentheses. Sections of the pore are indicated. Horizontal gray bars correspond to the approximate boundaries of the membrane, although the M1 helices are shielded from the membrane by M2 and M3. A Ca²⁺ ion is indicated. Red spheres mark the location of anomalous difference electron density attributed to iron, perhaps bound as (FeCl₆)^3- (Hou et al., 2012). The complex anion (IrCl₆)^3- also binds in these sites (Hou et al., 2012).