Figure 3.
Four diagrams of Orai1 protein structure and disease mutants. Panel A shows a top-view schematic of the four-helix arrangement, with helices 1, 2, 3, and 4 labeled and the central region highlighted in green. Panel B shows a side-view structural model with helices 1, 2, 3, and 4, with a magnified region highlighting residues S97, T184, H134, and L138. Panel C shows a structural model viewed from above, highlighting the positions of T92W and I138F. Panel D shows a magnified structural view with blue and yellow molecular structures and arrows indicating their positions and orientations relative to the surrounding helices.

Rearrangements at the inner interface due to Orai1 disease mutants. (A) Arrangement of the TM helices in the Orai1 hexamer. The inner interface between TM1 and TM2/3 is shown in green. (B) The left subunit shows a side view of an Orai1 subunit and the inner interface (green). The right subunit shows the location of the disease-causing Orai1 mutants. The inset shows a magnified view of the region. GoF mutants are depicted in red, LoF mutants in blue. Circles with numbers indicate the TMs, e.g., 1 corresponding to TM1. (C) Sketch of the Orai1 top view and location of the mutants L138F (yellow) and T92W (light blue). (D) Potential rearrangements of the TM helices, including rotation and outward movement of TM1 caused by the GoF mutants L138F (yellow) and T92W (light blue), respectively.

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