Figure 4.
Panel A: A top view diagram of the pore location in Orai1. The diagram shows four transmembrane segments labeled 1 to 4. Panel B: A side view diagram of the Orai1 pore, highlighted in green, including the pore resident disease-associated mutations. The diagram shows four transmembrane segments labeled 1 to 4 and highlights specific amino acid positions: V107, G98, and R91. Panel C: A schematic representation of the open Orai1 wild-type (WT) configuration. The diagram shows the normal pore hydration indicated in dark blue. Panel D: A model suggesting that the mutation of R91 to W leads to a steric plug of the pore, resulting in channel loss of function (LoF). The diagram shows the mutated configuration and highlights the steric plug model. Panel E: A model inferring that LoF occurs due to diminished hydration of the pore, indicated in light blue, after mutation of R91 to a W. The diagram shows the mutated configuration and highlights the hydration model.
Orai1 R91W LoF models. (A) Top view of the pore location in Orai1 (green). (B) Side view of the Orai1 pore (green) including the pore-resident disease-associated mutations. Circles with numbers indicate the TMs, e.g., 1 corresponding to TM1. (C) Schematic representation of the open Orai1 WT configuration. Dark blue indicates normal pore hydration. (D) This model suggests that the W introduced at position 91 leads to a steric plug of the pore, resulting in channel LoF. (E) Another model infers that LoF occurs due to diminished hydration of the pore, indicated in light blue, after mutation of R91 to a W.